Comparison between Diastolic Subendocardial Tissue Pressures Measured Directly or Calculated from Pressure-Flow Relations

Changes in intramyocardial tissue pressure modulate the relationship between coronary pressure and flow during the cardiac cycle. The present study compared the relation between measured and calculated diastolic subendocardial tissue pressure and coronary pressure at zero flow in anesthetized dogs after modulation of either coronary sinus (i.e. Fogarty catheter) or left ventricular intracavity (i.e. volume loading) pressure. Experiments were conducted in anesthetized, instrumented dogs;coronary pressure flow relations were constructed during pharmacologic vasodilatation and intramyocardial tissue pressure was measured using micromanometer pressure sensors. Elevated coronary sinus pressures did not affect subendocardial pressure-flow relations signifying that diastolic tissue pressure within this layer is the effective coronary back pressure. Higher left ventricular intracavity pressure did not affect either diastolic subendocardial tissue pressure or pressure flow relations within this layer. Results show a direct linear relation (y = 1.106x - 0.652;r2 = 0.59. P = 0.001) between measured and calculated diastolic subendocardial tissue pressure and coronary pressure at zero-flow over a wide range of pressures after either LV systemic or coronary sinus pressure modulation. Knowledge of back pressure in the subendocardium is useful for the evaluation of efficacy of cardiac interventions on myocardial perfusion particularly at the level of the microcirculation.

Ischemic Tolerance in Uremic Rabbits

Background: Cardiac complications after myocardial infarction are believed to be worse in the presence of comorbidities;we tested whether experimentally induced prolonged uremia exacer-bated myocardial necrosis in a rabbit preparation of ischemia-reperfusion injury. In addition, we examined if treatment with an angiotensin converting enzyme inhibitor (Enalapril, ENA, 3 mg/Kg, IV) could reduce post-ischemic myocardial damage. Methods: Prolonged uremia was induced by a two-stage subtotal nephrectomy and confirmed by marked increases in serum creatinine and urea levels;after 5 weeks, four groups of rabbits were exposed to 45-min acute coronary occlusion followed by 180-min reperfusion. In treated animals, ENA was administered 5-min before onset of coronary reperfusion. All data from uremic animals were compared with time-matched controls. Results: Cardiac hemodynamics was similar for all groups during the development of kidney failure;heart rate in uremic rabbits was significantly lower for the duration of ischemia-reperfusion. In this animal model, the absence of coronary collateral circulation provides a stable ischemic substrate for evaluation of cellular necrosis. Infarct size (expressed as percent risk zone size) was: control, 48 ± 16;uremia, 36 ± 5;control + ENA, 51 ± 19;and uremia + ENA, 41 ± 16;risk zone size was similar for all animals. Conclusion: The present findings are inconsistent with the view that post-ischemic cardiac injury is greater in animals with pre-existent uremia. In addition, we were unable to show a significant beneficial effect with an angiotensin converting enzyme inhibitor on infarct size in either control or uremic rabbits. It remains to be proven in animal models with comorbidities such as manifest kidney disease that ischemic tolerance can be substantially reduced by either pharmacologic or non-pharmacologic interventions.

Impact of Acute Ischemia-Reperfusion Injury on Left Ventricular Pressure-Volume Relations in Dogs

Objective: Ischemic conditioning (IC) limits myocyte necrosis after acute myocardial ischemia-reperfusion;however, controversy persists regarding its potential to attenuate LV contractile dysfunction. Pressure-volume (P-V) loop analysis, via the load-insensitive conductance catheter method, was used to evaluate LV contractility, diastolic function, and ventriculo-arterial coupling. The goal of this study was to evaluate the ability of IC to improve post-ischemic recovery of LV contractile function. Methods: Twelve anesthetized dogs were randomly distributed to either the IC or the non-IC group;all dogs were subject to 60-min acute coronary occlusion followed by 180-min reperfusion. IC consisted of 4 repeated cycles of 5-min occlusion and 5-min reperfusion of the left main coronary artery. LV P-V relations were constructed under steady-state conditions (by inferior vena cava occlusion) at the beginning and end of the experiments;P-V loops were acquired at different time points before and during ischemia-reperfusion. Results: During ischemia and reperfusion, dP/dtmax decreased significantly compared to baseline in both groups;dP/dtmin, an indicator of the rate of LV relaxation rate was not affected for either group. Significant changes in several parameters of LV function including LVEF, SW, tPFR, ESV, and EDV caused by ischemia were also identified;none of these negative effects were resorbed, even in part, during reperfusion. Conclusions: Diminished LV contractile efficiency during systole and diastole produced by ischemia-reperfusion did not improve with IC pre-treatment despite significant endogenous protection against tissue necrosis.

Effect of Acute Volume Loading on LV Function after Acute Cardiac Decentralization in Anesthetized Canines

The present study investigated the role of cardiac nerves on homeometric autoregulation in anesthetized dogs during acute volume loading. Ventricular pressure-volume loops (conductance catheter method) were constructed during acute volume loading with intact cardiac nerves (ICN) and after cardiac decentralization (DCN;bilateral ablation of thoracic vagosympathetic complexes, stellate ganglia and anterior and posterior ansae subclavia). Arterial pressure increased as expected after volume loading but no significant changes were observed for heart rate and other hemodynamic parameters. Coronary sinus venous oxygen content was also higher regardless of nerve status in response to the overall increase in cardiac work. Pressure-volume catheter data showed markedly higher end-systolic volumes after volume loading under ICN and DCN conditions;stroke volume (mL/beat) and stroke work (mL/mm Hg) were not changed but LV ejection fraction was significantly lower. End-diastolic volume and cardiac output did not change. In addition, systemic vascular resistance and tau were higher with volume loading but no differences between ICN and DCN were observed. These findings show that acute volume loading produces an immediate influence on LV function independent of cardiac nerve status.