Effects of perfusion pressure on energy and work of isolated rat hearts.

Abstract

A chemomechanical study of hypertrophied hearts of 6-month-old spontaneously hypertensive rats (SHR) and that of age-matched Wistar-Kyoto (WKY) rats was carried out, analyzing the response of the heart to steady-state changes in coronary perfusion pressure. The ratio of heart (dry)-to-body (wet) weight of WKY rats was 0.37±0.02 (10 3 ) and for SHR was 0.58±0.03 (1(T 3 ) (/7<0.01). In the apex-ejecting, isolated, pyruvate-perfused working hearts of WKY rats and SHR, coronary flow was constant when coronary perfusion pressure was set between 140 and 190 cm H 2 O (range of autoregulation). Coronary flow was perfusion pressure dependent when the coronary perfusion pressure was set below 110 cm H 2 O for both WKY rats and SHR. Cardiac output, developed pressure, rate of pressure development (dP/dt), and oxygen consumption were constant in the range of autoregulation but decreased in the direction of coronary flow when coronary flow was reduced by a drop in perfusion pressure. Similarly, the phosphorylation potential, phosphocreatine, adenosine triphosphate, and cyclic adenosine monophosphate were constant in the range of autoregulation but decreased directionally with coronary perfusion pressure below 110 cm H 2 O for both SHR and WKY rats. There was a significantly lower phosphorylation potential in SHR as compared with WKY rats when coronary perfusion pressure was reduced to 80 cm H 2 O. In the region of autoregulation, coronary flow and oxygen consumption were significantly less in SHR, although developed pressure was significantly greater at both high and low workloads. The importance of coronary perfusion pressure in SHR using the apex-ejecting working heart model was confirmed using other isolated perfused heart models (i.e., the Langendorff apex-vented heart model to simulate low workloads and the Langendorff isovolumic heart model to simulate high workloads). Furthermore, findings were not changed if FC-43 was added to the perfusate to facilitate delivery of oxygen to the myocardium and increase the viscosity of the perfusate. (Hypertension 1989;13:480-488) C oronary flow depends on perfusion pressure and vascular resistance.'-7 Vascular resistance depends on neurohormonal factors, myocardial contraction, myocardial metabolites, partial gas pressure, and alterations in the vascular endothelium. '-10 Both in situ 7 and in the isolated perfused heart 8 there is a range of coronary perfusion pressures from about 100 to 180 cm H 2 O 7 -8 where coronary perfusion pressure does not influence coronary flow; however, with values lower than 100 cm H 2 O, alterations in perfusion pressure result in a direct correlation between coronary flow

Oxygen reperfusion is limited in the postischemic hypertrophic myocardium

“…Although the contractility of the SHR heart is often overcompensated (14,24,39,53,61) and the energy utilization can be more efficient in LVH (45,61), why SHR hearts examined in the current study show higher baseline energy level is not clear. In fact, literature reports are mixed on the basal HEP level in moderate LVH: decreased, normal, or slightly increased (6,41,53,57,61).…”

“…Yet many studies have also demonstrated an altered energy metabolism in LVH and have suggested a cellular hypoxia (15,41,61,64). Consistent with possible O 2 limitation, a depressed O 2 consumption in the hypertrophic myocardium, especially under low perfusion pressure, has been reported (9,61).…”

“…The perfusate was delivered by a peristaltic pump (Rainin RP-1) to the top of the magnet, where the head pressure was set at 100 mmHg, a pressure high enough to allow hypertensive coronary vessels to autoregulate the flow (61). Coronary flow was measured by collecting the effluent perfusate returning from the heart.…”

“…In fact, literature reports are mixed on the basal HEP level in moderate LVH: decreased, normal, or slightly increased (6,41,53,57,61). In the case of human LVH patients, either no change (34, 48, 62) or varying degrees of reduction in the CrP/ATP ratio (21, 28) have been observed.…”

“…Pressure-induced hypertrophy leads to the loss of coronary flow reserve, narrowed arteriolar lumens, and increased minimal coronary vascular resistance, particularly in the subendocardial region (4,61). In effect, either the defect in the conductive (diffusion) and/or convective (flow) component of O 2 delivery can cause O 2 shortage in LVH.…”