Comparative effects of pacing-induced and flow-limited ischemia on left ventricular function.

Abstract

We compared left ventricular (LV) myocardial blood flow and function accompanying severe demand ischemia (rapid atrial pacing in the presence of critical bilateral coronary stenoses) and supply ischemia (complete bilateral coronary occlusion) of Hg, p=NS), and shifts in the LV diastolic pressure-dimension relation. Thus, although bilateral coronary occlusion produced quantitatively more extensive ischemia than a comparable duration of pacing-induced ischemia, abnormalities in systolic and diastolic function were qualitatively similar during a severe form of demand ischemia. Therefore, the ventricular response to ischemia does not simply depend on whether supply or demand ischemia is present but on a complex interaction between the duration, extent and severity, and type of ischemia elicited. (Circulation 1990;81:1380-1392

Mechanisms underlying ischemic diastolic dysfunction: relation between rigor, calcium homeostasis, and relaxation rate

“…Diastolic distensibility initially increased (LVEDP decreased from 10 to 8 Ϯ 0.5 mmHg, P Ͻ 0.005). This phenomenon has been postulated to result from either vascular decompression, i.e., a turgor effect, and/or intracellular metabolite accumulation (3,5,6,26,35). In a previous study (9) in isolated hearts, the degree of underperfusion used here resulted in intracellular acidosis (pH reduction to 6.2) and a 300% increase in inorganic phosphate.…”

“…Our results suggest that increased diastolic stiffness occurring in both supply and demand ischemia share a common subcellular mechanism (37,38), i.e., these states may not be qualitatively distinct but represent variations in the imbalance of myocardial oxygen supply relative to demand. This explains the clinical and experimental observation that the distinction between supply (predominant contractile dysfunction) and demand (predominant diastolic dysfunction) may not always be clear because either may result in mixed effects (3,26,35). The relative degrees of contractile and diastolic dysfunction elicited may be determined by the outcome of the balance among perfusion level, metabolic demand, and time.…”

“…In contrast, supply ischemia, e.g., during acute coronary thrombosis or experimental ligation, results in contractile failure and an initial increase in diastolic distensibility. Increased diastolic calcium has been reported to occur experimentally (6, 7, 18) but is postulated to be unable to express effects on diastolic tone because of accumulated intracellular metabolites, e.g., protons and inorganic phosphate, which reduce calcium sensitivity (3,5,26,35).We characterized the mechanisms responsible for diastolic dysfunction in the important clinical condition of supply ischemia. In isolated hearts, we reproduced physiological stable ischemia, simulating perfusion in an acute infarcted region with low coronary flow (without tachycardia).…”

“…The underlying etiology remains unclear, but persistently increased diastolic calcium (6,18), disturbed high-energy phosphate metabolism (16,36), and reduced relaxation velocity (7) have all been implicated. However, the precise nature of the ischemic insult, i.e., "supply" or "demand," may determine the mechanisms underlying diastolic dysfunction (3,5,15,26,35). Demand ischemia, where tachycardia occurs during moderately reduced coronary flow, characteristically results in an upward shift of the pressure-volume loop, i.e., increased diastolic stiffness, whereas contractile function remains preserved.…”

“…In contrast, supply ischemia, e.g., during acute coronary thrombosis or experimental ligation, results in contractile failure and an initial increase in diastolic distensibility. Increased diastolic calcium has been reported to occur experimentally (6,7,18) but is postulated to be unable to express effects on diastolic tone because of accumulated intracellular metabolites, e.g., protons and inorganic phosphate, which reduce calcium sensitivity (3,5,26,35).…”