Anesthetic management for the patients with cardiac transplant

With the advancement of medical technique and application of the new immunosuppressant agents, cardiac transplantation has become an effective treatment for end-stage heart disease caused by different reasons. The orthotopic procedure has been performed in many countries nowadays. Whether it is successful or not mainly depends on harvesting the denoted heart, operative technique and perioperative management.

Evaluation of the Management of Hyperlipidemia and Hypertension in an Outpatient Cardiac Transplant Clinic

Background: Allograft coronary artery disease (ACAD) is a common cause of morbidity and mortality post-orthotopic heart transplantation (OHT). ACAD progression may be reduced by modifying cardiovascular risk factors, such as hyperlipidemia and hypertension. We sought to evaluate the management of hyperlipidemia and hypertension among OHT recipients followed in an outpatient cardiac transplant clinic. Objective: The primary objective was to assess the proportion of OHT patients achieving both the recommended LDL target of <2.0 mmol/L and BP targets of <140/90 mmHg (or <130/80 mmHg for diabetics) in an outpatient cardiac transplant clinic. Methods: A cross-sectional retrospective analysis of the medical records of all adult OHT recipients actively followed in our outpatient cardiac transplant between January-March 2009. Results: Of the 193 patients included, both the low-density lipoprotein (LDL) cholesterol and blood pressure (BP) targets were achieved in 111 (57.5%) patients. The LDL target alone was achieved by 140 (72.5%) patients and the BP target alone by 153 (79.3%) patients. Statins were prescribed in 183 (94.8%) patients with a mean LDL of 1.81 mmol/L (±0.55). Angiotensin converting enzyme-inhibitors [ACE-I] (or angiotensin receptor blockers [ARB]) were prescribed in 154 (79.8%) patients, diltiazem in 101 (52.3%) patients, and both in 85 (44.0%) patients, with a mean BP of 124.2/77.8 mmHg (±13.6/8.2). Adverse reactions related to statins, ACE-inhibitors or diltiazem were uncommon and rarely resulted in drug discontinuation. Conclusions: Guideline recommended that LDL and BP targets are achievable in a significant proportion of OHT recipients. The high utilization rates of statins for dyslipidemia and ACE-I (or ARB) and diltiazem for BP were consistent with guideline recommendations for the prevention of ACAD. Despite concerns regarding the potential for pharmacokinetic drug interactions in OHT patients, the reported rates of any drug intolerance to these medications were low in our population.

Clinical analysis of recipients with survival over ten years after cardiac transplantation:a report of 13 cases

Objective To retrospectively analyze clinical management and follow - up of 13 recipients with survival over ten years after cardiac transplantation. Methods Thirteen male recipients underwent orthotopic heart transplantation between August 1995 and June 2001 in our center and received standard immunosuppressive

Interaction between castanospermine an immunosuppressant and cyclosporin A in rat cardiac transplantation

AIM: To investigate the interaction between castanospermine and cyclosporin A(Cs A) and to provide an explanation for it.METHODS: The alkaloid castanospermine was prepared from the seeds of Castanospermum austral consistently achieving purity. Rat heterotopic cardiac transplantation and mixed lymphocyte reactivity were done using genetically inbred strains of PVG(donor) and DA(recipient). For the mixed lymphocyte reaction stimulator cells were irradiated with 3000 rads using a linear accelerator. Cyclosporin A was administered by gavage and venous blood collected 2 h later(C_2). The blood levels of Cs A(Neoral) were measured by immunoassay which consisted of a homogeneous enzyme assay(EMIT) on Cobas Mira. Statistical analyses of interactions were done by an acceleratedfailure time model with Weibull distribution for allograft survival and logistic regression for the mixed lymphocyte reactivity.RESULTS: Castanospermine prolonged transplant survival times as a function of dose even at relatively low doses. Cyclosporin A also prolonged transplant survival times as a function of dose particularly at doses above 2 mg/kg. There were synergistic interactions between castanospermine and Cs A in the prolongation of cardiac allograft survival for dose ranges of Cs A by castanospermine of(0 to 2) mg/kg by(0 to 200) mg/kg(HR = 0.986; 95%CI: 0.981-0.992; P < 0.001) and(0 to 3) mg/kg by(0 to 100) mg/kg(HR = 0.986; 95%CI: 0.981-0.992; P < 0.001) respectively. The addition of castanospermine did not significantly increase the levels of cyclosporin A on day 3 or day 6 for all doses of Cs A. On the contrary, cessation of castanospermine in the presence of Cs A at 2 mg/kg significantly increased the Cs A level(P = 0.002). Castanospermine inhibited mixed lymphocyte reactivity in a dose dependent manner but without synergistic interaction. CONCLUSION: There is synergistic interaction between castanospermine and Cs A in rat cardiac transplantation. Neither the mixed lymphocyte reaction nor the metabolism of Cs A provides an explanation.

Efficacy of IABP in patients awaiting cardiac transplantation

Intra-aortic balloon pump (IABP)support is used in severalclinical situations.To determine its efficacy in patients with severe heartfailure awaiting cardiac transplantation,the experience at the Universityof Pittsburgh from May 1986 to October 1989 was reviewed.Of 392 patientson the waiting list,(16.3%) required IABP.All had previously been oninotropic support for varying periods of time.The ability to stabilize andto sustain the patient to cardiac transplantation was 75%.Twenty patients(31.3% of group) required and were provided more extensive mechanicalzsupport with either total artificial heart (n=ll) or left ventrieular assistdevice (n =9).Twenty-nine patients (45% of entire gronp) were able tohave the IABP removed prior to transplantation.Seventeen patients(26.6%)parameters demonstrated improvement with IABP.These data support IABPas a bridge to transplantation in patients with severe heart failure who havenot been stabilized on inotropie agents alone.These data also demonstratethat IABP support may only be required temporarily in a subgroup of pa-tients awaiting cardiac transplantation.

Classic Ehlers-Danlos syndrome and cardiac transplantation-Is there a connection?

Ehlers-Danlos syndrome(EDS)is a heterogeneous group of connective tissue disorders comprised of several types.Classic EDS is an autosomal dominant disorder with stretchable skin,delayed wound healing with poor scarring,joint hypermobility with subluxations or dislocations,easy bruisability,hernias,aneurysms and cardiac abnormalities.Advances in genomics technology using next-generation sequencing has led to the discovery of causative genes for connective tissue disorders,hereditary cardiomyopathies and cardiovascular diseases including several genes for connective tissue disorders.A 55 year-old male exhibited thin stretchable skin,atrophic scars,easy bruising,joint pain and dislocations requiring multiple knee surgeries and a Beighton hyperflexibility score of 6 out of 7.He was found to have a heterozygous missense COL5A1 gene variant involving exon 3 at nucleotide c:305T>A with an amino acid position change at p.lle102Asn consistent with classic EDS.He had a heart transplant at 43 years of age due to cardiac failure of unknown cause.This patient with classic EDS is brought to medical attention and should be of interest to cardiologists,heart transplant specialists and surgeons,particularly in individuals with unexplained cardiac failure and then diagnosed prior to surgical intervention to avoid poor wound healing,scarring and other tissue involvement(e.g.,vascular anomalies,blood pressure instability,aneurysms)as components of EDS.

Short- and Long-Term Outcomes of Cardiac Surgery in Kidney Transplant Recipients: A Review—Kidney Transplant and Cardiac Surgery

Background: Cardiovascular diseases remain the leading cause of death in kidney transplant patients and increasing proportion of these patients are referred to cardiac surgery. Data on short- and long-term outcomes of these patients are limited to single center reports with no randomized trials and no prospective studies published previously. The aim of this review was to report both short- and long-term outcomes of these patients. Methods: Literature review was conducted using three databases from inception to June 2022. Multiple search terms were used and limited to English language. Thirty-one relevant articles were included. Outcomes of interest were short-term mortality, long-term survival, renal allograft failure and infection in kidney transplant patients undergoing cardiac surgery. Results: Cardiac risk factors (diabetes mellitus, hypertension, hyperlipidemia) were prevalent in kidney transplant patients. 30-days mortality ranged across the studies from zero to 18.8%. The 1-year survival ranged from 71% - 97% and 5-years survival ranged from 31% - 95.7%. Commonest causes of death were cardiac and sepsis. Multiple predictors of mortality were reported. Postoperative acute kidney injury ranged from 0 - 74% with most of them being transient. Kidney graft failure ranged from 0 - 45% with 5-year kidney graft survival rates ranged between 37% - 80%. Post-operative infection rates ranged from 1% - 25% and the most common sites were pneumonia followed by septicemia and surgical site infections. Conclusion: Cardiac surgery can be performed in kidney transplant patients with good short- and long-term results.

Tacrolimus-related hypertrophic cardiomyopathy in an adult cardiac transplant patient

Left ventricular hypertrophy associated with the use of tacrolimus is a rare complication of solid organ transplantation in adult recipients. We present a cardiac transplant recipient who developed severe concentric left ventricular hypertrophy with congestive heart failure related to myocardial hypertrophy on tacrolimus. Hypertrophy improved when the drug was discontinued and replaced with sirolimus.

Cardiac arrest after graft reperfusion during liver transplantation

BACKGROUND: Cardiac arrest ( CA) during orthotopic liver transplantation (OLT) is rare but it threatens the lives of patients. The cause of perioperitive CA is not fully understood. We reported the occurrence of CA in 5 patients after unclamping of the vena cava and investigated the relationship between CA and associated variables. METHODS: Five patients with CA after graft reperfusion during OLT in our unit from November 1996 to September 2003 were retrospectively reviewed. Analyzed data included donor and recipient demographic data, and recipient operative and postoperative events. RESULTS: Five (2.1%) of 240 patients undergoing OLT experienced CA 5 minutes after graft reperfusion. Two patients died of resuscitation failure. Hyperkalemia and metabolic acidosis after revascularization were observed in some patients. The five patients had hypothermia and hypocalce-mia, and one had pulmonary embolism. CONCLUSIONS: CA is one of the syndromes after reperfusion. Many factors such as hyperkalemia, acidosis or pulmonary embolism combined with hypothermia and hy-pocalcemia during the operation seem to contribute to the occurrence of CA.

Tauroursodeoxycholic acid and 4-phenyl butyric acid alleviate endoplasmic reticulum stress and improve prognosis of donation after cardiac death liver transplantation in rats

BACKGROUND： Inevitable warm ischemia time before organ procurement aggravates posttransplantation ischemia- reperfusion injury. Endoplasmic reticulum （ER） stress is involved in ischemia-reperfusion injury, but its role in donation after cardiac death （DCD） liver transplantation is not clear and the effect of ER stress inhibitors, tauroursodeoxycholic acid （TUDCA） and 4-phenyl butyric acid （PBA）, on the prognosis of recipient of DCD liver transplantation remains unclear. METHODS： Male Sprague-Dawley rats （8-10 weeks） were randomly divided into control group： liver grafts without warm ischemia were implanted; DCD group： warm ischemia time of the liver grafts was 60 minutes; TUDCA and PBA groups： based on the DCD group, donors were intraperitoneally injected with TUDCA or PBA 30 minutes before the organ procurements. Serum aminotransferase levels, oxidative stress activation and expression of ER stress signal molecules were evaluated. Pathological examinations were performed. The survivals of the recipients in each group were compared for 14 days.RESULTS： Compared with the control group, DCD rats had significantly higher levels of serum aminotransferase at 6 hours, 1 day and 3 days after operation （P〈0.01, 0.01 and 0.05, respectively） and oxidative indices （P〈0.01 for both malondialdehyde and 8-hydroxy deoxyguanosine）, more severe liver damage （P〈0.01） and up-regulated ER stress signal expressions （P〈0.01 for GRP78, phos-eIF2al, CHOP, ATF-4, ATF-6, PERK, XBP-1 and pro-caspase-12）. All recipients died within 3 days after liver transplantation. Administration of TUDCA or PBA significantly decreased aminotransferase levels （P〈0.05）, increased superoxide dismutase activities （P〈0.01）, alleviated liver damage （P〈0.01）, down-regulated ER stress signal expressions （P〈0.01） and improved postoperative survivals （P〈0.01）. CONCLUSIONS： ER stress was involved with DCD liver trans- plantation in rats. Preoperative intraperitoneally injection of TUDCA or PBA protected ER stress and improved prognosis.

Cardiac evaluation of liver transplant candidates

Physicians previously thought that heart disease was rare in patients with end stage liver disease. However, recent evidence shows that the prevalence of ischemic heart disease and cardiomyopathy is increased in transplant candidates compared to most other surgical candidates. Investigators estimate that up to 26% of all liver transplant candidates have at least one critical coronary artery stenosis and that at least half of these patients will die perioperatively of cardiac complications. Cardiomyopathy also occurs in greater frequency. While all patients with advanced cardiac disease have defects in cardiac performance, a larger than expected number of patients have classical findings of dilated, restrictive and hypertropic cardiomyopathy. This may explain why up to 56% of patients suffer from hypoxemia due to pulmonary edema following transplant surgery. There is considerable controversy on how to screen transplant candidates for the presence of heart disease. Questions focus upon, which patients should be screened and what tests should be used. This review examines screening strategies for transplant candidates and details the prognostic value of common tests used to identify ischemic heart disease. We also review the physiological consequences of cardiomyopathy in transplant candidates and explore the specific syndrome of "cirrhotic cardiomyopathy".

Developing a donation after cardiac death risk index for adult and pediatric liver transplantation

AIM To identify objective predictive factors for donor after cardiac death(DCD) graft loss and using those factors, develop a donor recipient stratification risk predictive model that could be used to calculate a DCD risk index(DCD-RI) to help in prospective decision making on organ use.METHODS The model included objective data from a single institute DCD database(2005-2013, n = 261). Univariate survival analysis was followed by adjusted Cox-regressional hazard model. Covariates selected via univariate regression were added to the model via forward selection, significance level P = 0.3. The warm ischemic threshold was clinically set at 30 min. Points were given to each predictor in proportion to their hazard ratio. Using this model, the DCD-RI was calculated. The cohort was stratified to predict graft loss risk and respective graft survival calculated.RESULTS DCD graft survival predictors were primary indication for transplant(P = 0.066), retransplantation(P = 0.176), MELD > 25(P = 0.05), cold ischemia > 10 h(P = 0.292) and donor hepatectomy time > 60 min(P = 0.028).According to the calculated DCD-RI score three risk classes could be defined of low(DCD-RI < 1), standard(DCD-RI 2-4) and high risk(DCD-RI > 5) with a 5 years graft survival of 86%, 78% and 34%, respectively.CONCLUSION The DCD-RI score independently predicted graft loss(P < 0.001) and the DCD-RI class predicted graft survival(P < 0.001).

An improved model of heterotopic cardiac xenotransplantation from guinea－pig to rat

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Warm ischemia time and elevated serum uric acid are associated with metabolic syndrome after liver transplantation with donation after cardiac death

AIM To describe the prevalence of posttransplant metabolic syndrome(PTMS) after donation after cardiac death(DCD) liver transplantation(LT) and the pre-and postoperative risk factors.METHODS One hundred and forty-seven subjects who underwent DCD LT from January 2012 to February 2016 were enrolled in this study. The demographics and the clinical characteristics of pre-and post-transplantation were collected for both recipients and donors. PTMS was defined according to the 2004 Adult Treatment Panel-Ⅲ criteria. All subjects were followed monthly for the initial 6 mo after discharge, and then, every 3 mo for 2 years. The subjects were followed every 6 mo or as required after 2 years post-LT.RESULTS The prevalence of PTMS after DCD donor orthotopic LT was 20/147(13.6%). Recipient's body mass index(P = 0.024), warm ischemia time(WIT)(P = 0.045), and posttransplant hyperuricemia(P = 0.001) were significantly associated with PTMS. The change in serum uric acid levels in PTMS patients was significantly higher than that in non-PTMS patients(P < 0.001). After the 1 s t mo, the level of serum uric acid of PTMS patients rose continually over a period, while it was unaltered in non-PTMS patients. After transplantation, the level of serum uric acid in PTMS patients was not associated with renal function.CONCLUSION PTMS could occur at early stage after DCD LT with growing morbidity with the passage of time. WIT and post-LT hyperuricemia are associated with the prevalence of PTMS. An increased serum uric acid level is highly associated with PTMS and could act as a serum marker in this disease.

Intraoperative intracardiac thrombosis in a liver transplant patient

A 66-year-old female with cryptogenic cirrhosis complicated by ascites,hepatic encephalopathy,variceal bleeding and malnutrition with MELD of 34 underwent orthotopic deceased donor liver transplantation performed with piggyback technique.Extensive eversion thromboendovenectomy was performed for a portal vein thrombus which resulted in an excellent portal vein flow.The liver graft was recirculated without any hemodynamic instability.Subsequently,the patient became hypotensive progressing to asystole.She was resuscitated and a transesophageal probe was inserted which revealed a mobile right atrial thrombus and an underfilled poorly contractile right ventricle.The patient was noted to be coagulopathic at the time.She became progressively more stable with a TEE showing complete resolution of the intracardiac thrombus.

Continuous versus bolus cardiac output monitoring during orthotopic liver transplantation

BACKGROUND: Cardiac output monitoring is important for critical patients. This study aimed to determine the delayed response of continuous cardiac output (CCO) thermodilution measurement, whether CCO and bolus cardiac output (BCO) thermodilution agree sufficiently to be used interchangeably, and whether CCO monitoring is reliable for patients undergoing liver transplantation. METHODS: Thirteen patients undergoing liver transplantation without veno-venous bypass were studied (37-66 years old, weight 46-75 kg). Continuous and bolus thermodilution measurements were performed at predefined time points using an 'Opti-Q' SvO(2)/CCO monitor (Abbott Laboratories, North Chicago, IL, USA). Bias and 95% limits of agreement were calculated according to Bland and Altman analysis. The limits of agreement by which two methods are judged to be interchangeable were defined in advance as +/-(13%X BCO(mean)) L/min. The repeatability and relative error of CCO, and the differences between CCO and the mean of the two measurements were calculated. RESULTS: Cardiac output measurements yielded 196 data pairs with ranges of 1.9 to 17.9 L/min for CCO and 2.1 to 18.3 L/min for BCO. The response time of CCO was delayed in the early phases after caval clamping and after reperfusion. At most of the measurement points, bias and 95% limits of agreement were -0.18 +/- 1.91 L/min. 95% limits of agreement did not fall within the predetermined limits of agreement of +/- 1.14 L/min. The repeatability coefficient of CCO was 0.36 L/min and the relative error was 4.6 +/- 4.7%. The mean difference between CCO and the average of the two methods was -0.09 L/min (0.49 L/min). CONCLUSIONS: In patients undergoing liver transplantation, the delayed response of CCO limits its application during the early phases after caval clamping and after reperfusion of the graft. The two methods are not interchangeable even in hemodynamic stability. Continuous thermodilution monitoring, however, is reliable or acceptable for clinical purposes.

Impact of renal transplantation on cardiac morphological and functional characteristics in children and adults

AIM To compare the effects of renal transplantation on cardiac functions in children and adults.METHODS One hundred and ten patients attending the nephrology outpatient clinic were enrolled in this study and were divided into six groups. The first two groups consisted each of 30 renal transplant patients who had a successful renal transplantation more than six months, but less than one year. Group Ⅰ were less than 18 years and group Ⅱ were more than 18 years. The third and fourth groups, each were 20 chronic renal failure patients on regular hemodialysis. Again, group Ⅲ were less than 18 years and group Ⅳ were more than 18 years. Group Ⅴ and Ⅵ(The control Groups) consisted each of 5 subjects below and above 18 years of age, respectively with normal kidney functions. All patients were subjected to history and examination. The kidney functions and the hemoglobin were analyzed. Afterobtaining informed consent, echocardiography was done to all patients.RESULTS There was a statistically significant improvement(P < 0.0001) in all cardiac parameters. A regression in left ventricular end diastolic volume(LVED) both in children(4.7 ± 0.8 to 4.2 ± 0.5) and in adults(5.9 ± 0.7 to 4.9 ± 0.6) were found. There was a regression in left ventricular end systolic volume(LVES) both in children(3.1 ± 0.6 to 2.4 ± 0.4) and in adults(4.1 ± 0.9 to 3.1 ± 0.5). Fractional shortening improves both in children(32.6 ± 5.3 to 41.7 ± 7.6) and in adults(29.0 ± 6.6 to 36.5 ± 4.1). The improvement in ejection fraction(EF) was higher in children(59.7 ± 7.0 to 71.9 ± 6.1) than in adults(52.0 ± 12.5 to 64.8 ± 5.9). However, this degree of improvement(in children: 12.2 ± 5.1) did not show statistical difference(P-value 0.8), when compared to adults(12.7 ± 9.8). CONCLUSION After renal transplantation cardiac functions and morphology(EF/LVED/LVES) do improve markedly and rapidly in both children and adults.

Noninvasive Cardiac Testing—A New Routine in Evaluation of Renal Transplant Candidates

We report a case of a young kidney transplant candidate presented with severe and clinically completely asymptomatic mitral stenosis. The bedside Echocardiogram was helpful to establish the diagnosis. The surgery had to be postponed and the patient was referred to a cardiologist for the further workup. This case report provides solid evidence that the renal transplant candidates are a very unique group of patients with specific disease development course. Their preoperative workup cannot be based on widely used guidelines from American College of Cardiology and American Heart Association that are relying on clinical symptoms and presentation of cardiac disease. All physicians who are involved in the care of these patients and making decisions about their candidacy for the transplantation should take into account severity and very often asymptomatic presentation of the cardiovascular complications of the end stage renal disease. This case provides a good example of the importance of the multispecialty involvement and coordination in perioperative care for prospective kidney transplant candidates.

Expression of iNOSmRNA to prevent cardiac allograft vasculopathy after heart transplantation in rat

Objective Develop the model of post-transplant cardiac allograft vasculopathy (CAV) and prevent or treat CAV through Expression of iNOSmRNA.Methods Rat model of heterotopic heart transplantation was developed and three groups were divided as following: Comparison group, CsA group, iNSOmRNA group. Hearts were harvested at post-operative two weeks and four weeks and CAV was detected by immunohitochemical technique and in situ hybridization technique.Results iNOSmRNA group had no CAV develpment and synthetizing vast NO.Conclusion Expression of iNOSmRNA can prevent CAV development.

Assessment of cardiac output in liver transplantation recipients

BACKGROUND:Liver cirrhosis causes peculiar systemic hemodynamics,and accurate evaluation of systemic hemodynamic state is important for cirrhotic recipients who underwent living donor liver transplantation(LDLT). We investigated the clinical advantages of a novel non- invasive method for measuring systemic hemodynamic parameters using indocyanine green(ICG). METHODS:Twenty-eight LDLT recipients were evaluated. Simultaneous measurements of cardiac output(CO)using Swan-Ganz catheters and pulse dye densitometry(PDD) were performed every 12 hours after LDLT.A total of 155 sets of simultaneous CO measurements were obtained. RESULTS:The CO values obtained by PDD correlated well with those obtained by the invasive catheter technique.In addition,none of the recipients developed any side-effects, and we verified the safety of repeated ICG injections.ICG is safe,even for repeated use over time in the same recipient. Moreover,PDD can measure the blood volume(BV).CONCLUSIONS:Since the cirrhotic systemic hemody- namics characterized by high CO and large BV remains, even after LDLT,the ability to measure CO and BV in a non-invasive,simple and real-time manner using PDD has advantages for cirrhotic LDLT recipients.