Paradoxical Effects of Catecholamines and Calcium on Myocardial Function in Moderate Hyperthermia

Summary

Considerable elevations of left ventricular diastolic pressure in relation to cardiac volume are often observed in clinical situations such as angina pectoris, acute myocardial infarction and low output syndrome after cardiopulmonary bypass. Both a calcium-related increase in resting tension and myocardial contracture have been held responsible for the altered left ventricular diastolic properties under hypoxic conditions. However, an experimental approach suggesting evidence for the occurrence of a calcium-induced diastolic tone in the intact beating heart with reference to changes in hemodynamics and myocardial energetics has not been presented so far.

The situation of a marked, but reversible increase in left ventricular diastolic pressure (18 to 60 mmHg) after catecholamine stimulation in moderate hypothermia (31 ± 0.5 °C) was systematically studied using a clinical catheterization technique in 10 intact dogs. An energy demand for the maintenance of active diastolic wall tension was estimated from diastolic hemodynamics. Sixty-three steady states were analyzed.

The occurrence of a reversible increase in left ventricular diastolic pressure relative to volume was reproducible in all experiments. This catecholamine-induced myocardial failure was characterized as follows: Dramatic elevation of ventricular diastolic pressure, depressed systolic performance, and increased myocardial oxygen consumption as compared to controls. Calcium intensified these changes due to a marked negative inotropic effect. The energy demand of approximated diastolic wall tension ranged between 1 and 4 ml O₂/ min- 100 g with a mean of 2.01 ± 0.13 ml O₂/min · 100 g at a corresponding left ventricular enddiastolic pressure of 31 ± 1.9 mmHg.

The occurrence of a reversible catecholamine-induced myocardial failure in hypothermia is probably caused by an intracellular calcium overload due to increased influx and decreased calcium sequestration. Since this reaction was intensified by the application of calcium it may represent a calcium-induced diastolic tone of the heart having unfavorable effects on both the systolic and diastolic ventricular function and on myocardial energetics.

Key words

Catecholamines - Calcium - Hypothermia - Myocardial function - Myocardial energetics - Diastolic tone