This study was conducted to compare separately the chronic effects of high blood levels of ethanol and acetaldehyde on the metabolism of the heart. Levels of ethanol and acetaldehyde were altered by administration of either 4-methylpyrazole (4-MP), a potent alcohol dehydrogenase inhibitor, or pargyline (PAR), a monoamine oxidase inhibitor that markedly increases acetaldehyde levels in the blood following ethanol administration. Measurements were made in rats consuming ethanol for three to four weeks. Mitochondrial respiration, in vitro contractility of glycerinated heart muscle fibers, and myocardial protein synthesis were determined. As compared to animals receiving only ethanol, administration of either-4-methyl-pyrazole or pargyline plus ethanol resulted in more severe damage to mitochondrial respiration and myocardial protein synthesis. The data illustrate that both acetaldehyde and ethanol in high concentrations can cause severe damage to myocardial metabolism.

Acetaldehyde↗

PubMedDate not supplied

The relationship between myocardial oxygen consumption and total work obtained by a new left ventricular model.

The relationship between myocardial oxygen consumption (MVO2) and left ventricular work was examined experimentally, assuming that the left ventricle is equivalent to an electrical current source generator consisting of parallel source resistance (Ri) and constant generator current (I0). The internal and external work can be calculated as (Ri X I1(2)) and (Rp X I2(2)) in this model, where I1 is current of source resistance, Rp is peripheral resistance and I2 is cardiac output. The experiments were performed with a blood-perfused isolated ejecting canine heart preparation in which the hydraulic model, simulated to an aortic input impedance, was attached to the aortic root. The peripheral resistance was changed in a stepwise fashion and left ventricular pressure, cardiac output and MVO2 were measured. The calculated total work showed a close linear correlation with the MVO2, which suggested that the left ventricle can be regarded as a current source generator and the total work as a main mechanical factor in determining the MVO2.

Animals↗

PubMedDate not supplied

Pressure-length loop in the ischemic segment during left circumflex coronary artery stenosis and its modification by afterload reducing in excised perfused canine hearts.

By using excised perfused heart preparations, we investigated the regional myocardial functions in the presence of a flow-limiting coronary stenosis of the left circumflex coronary artery (LCX) (approximately low reduction of pre-ischemic control), as well as global cardiac functions during afterload reducing, while keeping left ventricular end-diastolic pressure (LVEDP) and heart rate constant. After inducing the LCX stenosis, cardiac output (CO), peak left ventricular pressure (peak LVP) and stroke work (SW) decreased from pre-ischemic control values, i.e., 81.1 +/- 3.2%, p less than 0.005, 88.1 +/- 3.8%, p less than 0.02 and 72.2 +/- 5.7%, p less than 0.005, respectively (n = 7), whereas pressure-length (P-L) loop areas changed as follows; ischemic control values of the left anterior descending coronary artery (LAD) and LCX regions were 96.6 +/- 6.0%, n.s. and 72.6 +/- 9.0% of pre-ischemic control, p less than 0.02, respectively. Following afterload reducing with LCX stenosis, CO increased gradually, while the ischemic regional function started to further aggravate, and the initial point of further ischemic aggravation obtained in this experiment occurred at 63.5 +/- 6.9 mm Hg of mean aortic pressure (AoP). These results suggested that the increase of total cardiac function such as CO following afterload reducing was probably induced at the expense of aggravated regional ischemia. Therefore it was concluded that the treatment of ischemic myocardium by reducing afterload pressure should be done very carefully.

Animals↗

PubMedDate not supplied

Effects of OPC-8212, a new positive inotropic agent, and dobutamine on left ventricular global and ischemic regional functions and coronary hemodynamics under coronary artery stenosis.

We have investigated the effects of OPC-8212, a new positive inotropic agent, and dobutamine, a known cardioselective inotropic agent, on global left ventricular (LV) and ischemic regional functions in 14 excised canine hearts with a flow-limiting stenosis of the left circumflex coronary artery (LCX) (i.e., 20-25% of control flow). OPC-8212 infusion (n = 7) under LCX stenosis improved cardiac depression [i.e., peak LV dP/dt increased from 1,295 +/- 143 mm Hg/s to 2,669 +/- 266 mm Hg/s (mean +/- SEM) (p less than 0.001)], while myocardial ischemic injury, assessed by myocardial CO2-tension and electrocardiogram (ECG)-ST changes, improved (i.e., delta CO2-tension and ECG-ST deviation decreased from 21.1 +/- 3.6 mm Hg and 3.8 +/- 0.6 mV to 13.3 +/- 2.8 mm Hg (p less than 0.01) and 2.0 +/- 0.7 mV (p less than 0.05), respectively). On the other hand, dobutamine infusion (n = 7) further increased myocardial CO2-tension and ECG-ST deviation [i.e., delta CO2-tension and ECG-ST deviation increased from 14.4 +/- 4.2 mm Hg and 2.5 +/- 1.2 mV to 29.0 +/- 6.0 mm Hg (p less than 0.01) and 4.9 +/- 1.0 mV (p less than 0.01), respectively]. At the same time, peak LV dP/dt clearly improved, but to a lesser degree; from 1,425 +/- 153 mm Hg/s to 2,393 +/- 245 mm Hg/s (p less than 0.001). There was also an increase in percent systolic segment shortening of each corresponding area as with OPC-8212.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗