Mechanical circulatory support

Currently, almost five million Americans and 23 million people worldwide are living with congestive heart failure (CHF), with 2 million new cases diagnosed each year. The etiology is mostly ischemic, idiopathic, or viral, and more than $36 billion is spent each year on the care of congestive heart failure patients. Treatment of advanced CHF takes three forms: medical therapy, surgical therapy and cardiac replacement. Medical therapy, including inotropes and vasodilators, relieves symptoms by reducing cardiac work and increasing myocardial contractility. This has helped improve quality of life, but mortality remains unaffected. Surgical therapy, including revascularization, ventricular restoration and valve replacement/repair, relieves symptoms and improves function, but in most cases does not stop the underlying disease process from progressing. When conventional medical or surgical therapies are exhausted, cardiac assist or replacement, including ventricular assist device (VAD), heart transplant or a total artificial heart (TAH) may become the only therapeutic options. This article will not discuss the use of extracorporeal membrane oxygenation for cardiac support that is described in an additional article in this issue of Organogenesis.     

Acute circulatory support.

Numerous drugs can increase cardiac output, thereby improving tissue oxygen delivery, but often they do this at the expense of increasing myocardial oxygen demand. This may be critical when cardiac function is substantially impaired or ischaemia is the precipitating cause. Using polypharmacy to substantially improve cardiovascular status requires detailed knowledge of the pharmacodynamics and interactions of the available agents so that they may be tailored to the individual patient. In some settings combinations of inotropes and vasodilators may be desirable to minimise cardiac workload. In other instances vasopressors may be necessary to urgently restore a minimum perfusion pressure. This paper reviews the use of this group of drugs as well as the mechanical assist devices that may be used when drugs fail.     

Coronary circulatory pressure gradients

The pressure gradients of the canine coronary circulation were measured in 37 dogs during control and following eight interventions: left stellate ganglion or left vagosympathetic trunk stimulation, as well as isoproterenol, acetylcholine, noradrenaline, adenosine, phenylephrine, or adrenaline infusions. During control, pressure gradients in the epicardial coronary arteries (measured from the aorta to coronary artery branch) were 15.2 +/- 1 mmHg (1 mmHg (1 mmHg = 133.32 Pa) during systole and 10.6 +/- 1.5 mmHg during diastole. Adrenaline increased this systolic gradient, while acetylcholine and phenylephrine decreased it. In contrast, the pressure gradients in the small coronary arteries (from the branch of an epicardial artery to the pressure in an obstructed coronary artery) were 56 +/- 1.3 mmHg during systole and 63.7 +/- 1.3 mmHg during diastole. These gradients were increased by phenylephrine during both systole and diastole, noradrenaline and adrenaline during diastole and decreased by isoproterenol (systolic), left vagosympathetic trunk stimulation (diastolic), acetylcholine (systolic and diastolic), and adenosine (diastolic). The microcirculation and small vein gradients during control were 16.4 +/- 1.2 mmHg during systole and 8.5 +/- 0.8 mmHg during diastole. Decreases in this gradient were produced by isoproterenol, acetylcholine, and adenosine during systole and adenosine during diastole. These observations are consistent with the concept that the coronary circulation has considerable regulatory capacity in all of its component parts. Specifically, epicardial arteries appear to function as both conduits and as resistance vessels, small arteries as major resistance vessels, and the microcirculation and small veins as both capacitors and resistors.     

Prostaglandin metabolism during circulatory shock

The rates of metabolic degradation and the patterns of metabolite formation of tritium-labeled prostaglandins E₂ and F_2α were assessed in vitro in tissues obtained from normal rabbits and from rabbits subjected to hemorrhagic or endotoxic shock. Normal rabbit tissues metabolized prostaglandin E₂ at the following rates: renal cortex 479 ± 34, liver 389 ± 95, and lung 881 ± 93 pmol of PGE₂ metabolized/mg soluble protein per min at 37°C (mean ± S.E.). Prostaglandin F_2α metabolism proceeded in normal animal tissues at rates of 477 ± 39, 324 ± 95, and 633 ± 69 pmol of PGF_2α metabolized/mg soluble protein per min for renal cortex, liver and lung, respectively. There were no significant differences between these rates of PGE₂ and PGF_2α metabolism when compared to rates in tissues obtained from animals subjected to either hemorrhagic or endotoxic shock. In addition, no significant differences were observed between the rate of PGE₂ metabolism and that of PGF_2α metabolism for any tissue. However, the lung was able to metabolize PGE₂ and PGF_2α significantly more rapidly than the liver, and to degrade PGE₂ at a significantly greater rate than the renal cortex. Although slightly different patterns of metabolite production were observed between lung and kidney homogenates, only the liver metabolized prostaglandins almost exclusively to more polar metabolites. While hemorrhagic or endotoxic shock induced slight changes in the patterns of PGE₂ metabolite formation in all three tissues studied, PGF_2α metabolite formation patterns were not significantly altered by circulatory shock. Thus, prostaglandin metabolism is not significantly impaired during the first 2 h of hemorrhagic or endotoxic shock in rabbit tissues. Therefore, impairment of prostaglandin metabolism is not the major factor responsible for the early increase in circulating prostaglandin concentrations in these forms of shock.     

Orthostatic circulatory disorders in schoolchildren

The circulation control in syncope has been studied in schoolchildren by means of the Kentavr computer system. The functional tilt table test has been used to study the response to orthostasis in healthy students (control) and adolescents with lipothymia. It is concluded that the passive orthostatic test is efficient for differential diagnosis of the type of faint and is important for comprehensive examination of schoolchildren.     

Systemic circulatory effects of pentagastrin

Effects of pentagastrin on systemic circulation were studied in anesthetized cats. Systemic arterial, central venous and portal pressure were monitored with electromanometers and blood flow through the superior mesenteric artery, common carotid artery, femoral artery and ascending aorta were measured with an electromagnetic blood flow meter. Pentagastrin injected intravenously at a doses of 2.0, 4.0 and 8.0 micrograms/kg induced a dose-dependent fall in arterial pressure, heart rate and cardiac output, increased mesenteric blood flow, decreased common carotid artery blood flow, did not change femoral artery blood flow and slightly rose central venous pressure. Atropine blocked observed effects. After repeated injections of the peptide, tachyphylaxis quickly developed. The obtained results indicate that pentagastrin influences general hemodynamics probably via interaction with cholinergic receptors.