[Systemic and coronary haemodynamic effects of dobutamine and norepinephrine during metabolic acidosis]. / Wirkungen von Dobutamin und Noradrenalin auf den Systemkreislauf und die Sauerstoffversorgung des Myokards bei metabolischer azidose.

The effects of clinical doses of dobutamine (5 microgram/kg x min) and norepinephrine (0.2 microgram/kg x min) on systemic haemodynamics and coronary circulation were studied during normal pH and during metabolic acidosis (pH 7.0) induced by hydrochloric acid in 9 anaesthetized closed chest dogs. Metabolic acidosis per se failed to show any significant depression of cardiac function, indicating that animals with intact sympathoadrenal system are highly resistant to acidaemia. Our results further demonstrated that a significant circulatory response to clinical doses of dobutamine and norepinephrine was still present during metabolic acidosis. However, the increase in cardiac output, max dp/dt and mean arterial pressure after dobutamine was found to be significantly reduced at low pH-values, whereas the vasopressor response to norepinephrine was not affected. From these results it may be speculated that metabolic acidosis differently influences the responsiveness of alpha- and beta-adrenergic receptors. Finally our results show that metabolic acidosis did not compromise the coronary adjustment to catecholamine-induced increases in myocardial oxygen demand.

Circulatory pattern and duration of action of naloxone in dogs with and without opioid pretreatment.

We investigated the circulatory pattern of naloxone reversal after high-dose fentanyl infusion in dogs. Within 1 min there was a sudden decrease in total peripheral resistance with a concomitant increase in stroke volume index. All other parameters changed back in direction of pre-fentanyl values in various degrees with peak effects in about 3-7 min. The persistency of reversal was different for individual parameters, but 20 min after injection of naloxone almost all changes induced by antagonisation of narcotic activity had returned to pre naloxone levels. In a control series with animals not pretreated with opioid, naloxone was shown to have no specific pharmacologic action of its own.

[A comparison of cardiovascular effects of dobutamine and dopamine (author's transl)]. / Ein Vergleich der kardiovaskulären Wirkungen von Dobutamin und Dopamin.

The influences of dobutamine and dopamine 5-40 microgram/kg-min intravenously on hemodynamics and myocardial oxygen consumption were investigated in closed chest dogs (n=9). Heart rate (HR), cardiac index (CI), stroke volume (SVI), mean aortic pressure (MAP), pulmonary artery pressure (PAP), central venous pressure (CVP), left ventricular enddiastolic pressure (LVEDP), myocardial blood flow (MBF) and maximum dp/dt (dp/dtmax) were measured. Total peripheral resistance (TPR), coronary vascular resistance (CVR), myocardial oxygen consumption (MVO2), efficiency of heart work (EME), the ventricular volumes (EDV, ESV) and the ejection fraction (EF) were calculated. When dopamine was infused, the cardiac output rose mainly by an increase of heart rate. During dobutamine an increase of stroke volume and ejection fraction was involved in the improvement of cardiac output. Heart rate and mean aortic pressure increased to a greater extent by dopamine. Dobutamine and dopamine increase myocardial blood flow and oxygen consumption. The comparatively slight effects of dobutamine on afterload and heart rate resulted in smaller increases in myocardial oxygen consumption. The efficiency of external heart work was increased by dobutamine at the doses of 5 microgram and 10 microgram/kg-min. In the higher dose range external myocardial efficiency decreased under dopamine and dobutamine. Load data and heart rate indicate that a greater inotropic effect of dobutamine compared with equal doses of dopamine is involved in the increase of dp/dtmax. The results are discussed in relation to a clinical use of dobutamine and dopamine.

[Influence of modern inhalation anaesthetics on haemodynamics, myocardial contractility, left ventricular volumes and myocardial oxygen supply (author's transl)]. / Hämodynamik, Myokardkontraktilität, Ventrikelvolumina und Sauerstoffversorgung des Herzens unter verschiedenen Inhalationsanaesthetika.

The cardiocirculatory responses to equianaesthetic concentrations (MAC 0.5 and MAC 1.0 plus 67% N2O) of halothane, methoxyflurane, enflurane and isoflurane were studied in a total of 35 closed-chest dogs during ventilation controlled to produce normocapnia. Each anaesthetic produced a dose-related decrease in mean arterial pressure and in values reflecting cardiac function. These included cardiac output, stroke volume, left ventricular max dp/dt and ejection fraction. Isoflurane seemed slightly less depressant to the heart than the other 3 anaesthetics. Total peripheral resistance remained nearly unaffected during halothane and methoxyflurane anaesthesia but decreased significantly with MAC 1.0 enflurane and isoflurane. There was no change in heart rate at low anaesthetic concentrations. The deeper levels of anaesthesia were associated with moderate increases in heart rate. In spite of the obvious depression of myocardial contractility there was a fall in pulmonary artery and left ventricular end-diastolic pressures and in left ventricular end-diastolic volumes with each of the agents. We take this as an expression of decreased ventricular filling resulted from pooling of blood in peripheral capacitive vessels. With the exception of isoflurane, each of the other three anaesthetics reduced coronary blood flow. Coronary vascular resistance was not substantially influenced by halothane and methoxyflurane, but decreased with MAC 1.0 enflurane and isoflurane. Myocardial oxygen availability was always found to be adequate. Isoflurane even produced a significant rise in coronary venous oxygen saturation indicating coronary vasodilation. Parallel with the depression in cardiac performance and blood pressure as two of the main predictors of energy demand, myocardial oxygen consumption was found to be significantly reduced by each of the anaesthetics. The ratio of the external work of the left ventricle to its oxygen consumption indicated that myocardial efficiency deterioated. The clinical implications are discussed.

[The effects of the vasodilator nitroprusside on haemodynamics and myocardial oxygen consumption during drug induced myocardial depression (author's transl)]. / Kardiovaskuläre Wirkungen von Natriumnitroprussid während einer Myokarddepression.

The effect of the vasodilator nitroprusside (NP) on haemodynamics and myocardial oxygen consumption during drug induced myocardial oepression was examined in dogs (n = 7). The investigations were performed on closed chest dogs lightly anaesthetized with piritramide and N2O/O2 (ratio 2:1) under controlled ventilation and after beta-adrenergic blockade (1.5 mg/kg propranolol). After a loading dose and a continuous infusion of 0.3 mg/kg X min of pentobarbitone left ventricular maximum dp/dt was reduced to 50% of the control level, which was taken for granted as a standardized myocardial depression. Using an infusion of NP at a mean rate of 7 microgram/kg X min mean arterial pressure was then lowered to 80 mmHg for 20 min. The vasodilator therapy led to an increase in cardiac output and in stroke volume by 16%. Since the calculated endsystolic volume of the left ventricle decreased simultaneously (19%), the ejection fraction increased from 38% to 46%. There was also a significant reduction in left ventricular enddiastolic pressure (46%), which is supposed to result from the combined effects of an improved myocardial performance, a pooling of blood in peripheral vessels (indicated by decreases in enddiastolic volume by 6%, in mean pulmonary arterial pressure by 25% and in central venous pressure by 45%) and an increased ventricular compliance. Since the myocardial wall tension, a major determinant of myocardial energy demand, was lowered by increased ventricular compliance and reduced pre- and afterload, the oxygen consumption of the heart decreased by 22%. The smaller demand was supplied by an unchanged coronary blood flow. The narrowing of the a-v oxygen difference of the heart indicated a coronary dilatation (10%). The results obtained from this study support the clinical observations that NNP may improve an imbalanced ratio between myocardial oxygen supply and demand, in patients with impaired cardiac performance.

[Doxapram-induced changes in circulation and myocardial efficiency (author's transl)]. / Kreislaufstimulation durch Doxapram

The effects of Doxapram 2.0 mg/kg intravenously on circulation and myocardial oxygen supply were studied in 9 anaesthetized closed chest dogs. Immediately after Doxapram increases in heart rate (maximum+40.5%, 1st min), mean aortic pressure (+49%, 3rd min), cardiac index (+18%, 3rd min), total peripheral resistance (+32%, 3rd min), pulmonary arterial pressure (+48%, 1st min), left ventricular end-diastolic pressure (+79%, 1st min), myocardial blood flow (+38%, 3rd min), myocardial oxygen consumption (+74%, 1st min) and left ventricular work (+76%, 1st min) were observed. The changes in heart rate, mean aortic pressure, myocardial blood flow, myocardial oxygen consumption and heart work were persistent up to 20 min after Doxapram 2.0 mg/kg intravenously. Max dp/dt, coronary vascular resistance and the myocardial efficiency were not influenced after Doxapram.

Dopamine effects on circulation and myocardial oxygen supply.

We measured the action of dopamine given intravenously at dosage ranging from 2.5 to 320 micrograms/kg per min in closed chest anaesthetized dogs. Dopamine produced a dose-dependent increase in heart rate, cardiac index, mean arterial pressure, total peripheral resistance, pulmonary artery pressure, left ventricular end diastolic pressure, coronary flow and myocardial oxygen consumption. At dopamine dosage of 80-320 micrograms/kg per min, the coronary vascular resistance, the stroke volume index, the efficiency of heart work and the central venous pressure are all decreased. The maximum effect of dopamine on the circulation was seen at a dose between 40 and 80 micrograms/kg per min.