H. B. van Wezel

Perioperative hyperinsulinaemic normoglycaemic clamp causes hypolipidaemia after coronary artery surgery

BACKGROUND Glucose-insulin-potassium (GIK) administration is advocated on the premise of preventing hyperglycaemia and hyperlipidaemia during reperfusion after cardiac interventions. Current research has focused on hyperglycaemia, largely ignoring lipids, or other substrates. The present study examines lipids and other substrates during and after on-pump coronary artery bypass grafting and how they are affected by a hyperinsulinaemic normoglycaemic clamp. METHODS Forty-four patients were randomized to a control group (n=21) or to a GIK group (n=23) receiving a hyperinsulinaemic normoglycaemic clamp during 26 h. Plasma levels of free fatty acid (FFA), total and lipoprotein (VLDL, HDL, and LDL)-triglycerides (TG), ketone bodies, and lactate were determined. RESULTS In the control group, mean FFA peaked at 0.76 (sem 0.05) mmol litre(-1) at early reperfusion and decreased to 0.3-0.5 mmol litre(-1) during the remaining part of the study. GIK decreased FFA levels to 0.38 (0.05) mmol litre(-1) at early reperfusion, and to low concentrations of 0.10 (0.01) mmol litre(-1) during the hyperinsulinaemic clamp. GIK reduced the area under the curve (AUC) for FFA by 75% and for TG by 53%. The reduction in total TG was reflected by a reduction in the VLDL (-54% AUC) and HDL (-42% AUC) fraction, but not in the LDL fraction. GIK prevented the increase in ketone bodies after reperfusion (-44 to -47% AUC), but was without effect on lactate levels. CONCLUSIONS Mild hyperlipidaemia was only observed during early reperfusion (before heparin reversal) and the hyperinsulinaemic normoglycaemic clamp actually resulted in hypolipidaemia during the largest part of reperfusion after cardiac surgery.

Antihypertensive drug treatment in the perioperative period

YPERTENSION, a major risk factor for coronary artery disease (CAD), congestive heart failure (CHF), stroke, and kidney damage is widespread, not particularly difficult to discover and, in the majority of cases, responsive to treatment. It is, therefore, not surprising that anesthesiologists, as well as various other types of physicians who do not primarily treat hypertension, will encounter hypertensive patients who are on drug treatment. Treatment of hypertensive disease has made tremendous progress in the rather short period of the past four decades, although several problems remain unso1ved.l Essential hypertension comprises at least 90% of cases of hypertensive disease. This major form of the disease, which causes no subjective symptoms for a long time, is usually treated by drugs, although changes in life-style (normalization of body weight, restricted intake of sodium and ethanol, regular physical exercise, stopping smoking) continue to be an important basis of intervention. Secondary hypertension, (approximately 10% of cases) caused by disorders such as renal artery stenosis, Conn’s disease, coarctation of the aorta, or pheochromocytoma, is predominantly treated by surgery, although drug treatment usually precedes surgical intervention. Drug treatment of essential hypertension has developed in a most sophisticated manner and a variety of different types of drugs are available at present. Most of the older drugs that interact with the sympathetic nervous system, like the ganglioplegic agents, postganglionic neuron blockers, and reserpine have lost much of their importance. A similar tendency is being observed for centrally acting cr2-adrenoceptor agonists like clonidine and a-methylDOPA (via its inactive metabolite o-methyl norepinephrine).* However, classical drugs like B-blockers and diuretics continue to be a mainstay of antihypertensive treatment. Calcium channel antagonists, ACE-inhibitors, postsynaptic ai-adrenoreceptor blocking agents, and hybrid (multifactorial) drugs have been added as valuable therapeutics to the armamentarium of antihypertensive drugs. Essential hypertension and ischemic heart disease frequently occur simultaneously. Because hypertension is

Chronic cardiac denervation affects the speed of coronary vascular regulation

OBJECTIVE We tested the hypothesis that the rate of adaptation of coronary metabolic vasodilatation and autoregulation is modulated by the cardiac nerves. METHODS Anaesthetised dogs (seven innervated (control) and seven with denervated hearts) were subjected to controlled pressure perfusion of the left main coronary artery. Heart rate was controlled by pacing. RESULTS The steady state autoregulation curves and metabolic regulation curves were similar in the two groups. A sudden increase or decrease in heart rate was associated with a faster response (22% shorter half-times) in the innervated than the denervated dogs (P < 0.001). A sudden increase or decrease in coronary arterial perfusion pressure was associated with a slower response (24% longer half-times) in the innervated than the denervated hearts (P < 0.005). CONCLUSIONS We conclude that the speed of response to metabolic and perfusion pressure changes is partly mediated by cardio-cardiac reflexes. Reflex coronary vasodilatation appears to reinforce the metabolic vasodilatation of a heart rate increase and oppose the vasoconstriction in response to increased perfusion pressure.

Effects of dobutamine and enoximone on transmitral and pulmonary venous flow characteristics in patients with left ventricular dysfunction after coronary artery bypass grafting

OBJECTIVES To assess the effects of dobutamine and enoximone on transmitral (TMF) and pulmonary venous flow (PVF) characteristics. DESIGN Prospective and randomized. SETTING A university hospital intensive care unit. PARTICIPANTS Thirty patients with moderate left ventricular dysfunction after coronary artery bypass grafting (CABG). INTERVENTIONS Patients received either dobutamine, 10 micrograms/kg/min, or enoximone, 20 micrograms/kg/min, for the treatment of a low cardiac index (CI) (< 2.2 L/min/m2). MEASUREMENTS AND MAIN RESULTS Both drugs significantly (p < 0.05) increased CI from 1.91 +/- 0.17 (dobutamine) and 1.97 +/- 0.17 (enoximone) at baseline to 2.86 +/- 0.70 and 2.84 +/- 0.39 L/min/m2, respectively. Compared with the enoximone (enox)-treated group, the administration of dobutamine (dob) resulted in significantly (p < 0.05) greater increases in mean arterial pressure (dob: 18 +/- 9% v enox: -2 +/- 7%), heart rate (dob: 24 +/- 13% v enox: 3 +/- 5%) and pulmonary artery pressure (dob: 5 +/- 10% v enox: -4 +/- 9%). In contrast, the increase in stroke volume index was significantly less in the dobutamine-treated group (dob: 22 +/- 27% v enox: 41 +/- 21%). The TMF indices, peak E, and peak A wave increased significantly (p < 0.05) after both dobutamine (baseline: 37.3 +/- 6.7 and 41.1 +/- 9.3; max dose: 42.4 +/- 4.3 and 49.0 +/- 10.2 cm/s) and enoximone (baseline: 36.2 +/- 7.5 and 44.2 +/- 10.9; max dose: 40.5 +/- 5.0 and 49.4 +/- 12.1 cm/s) without significantly altering the E/A ratio. Only dobutamine significantly (p < 0.05) decreased isovolumic relaxation time from 109 +/- 24 to 94 +/- 21 ms. There was no significant change in isovolumic relaxation time between the dobutamine (-12% +/- 17%)- and the enoximone (-4% +/- 21%)- treated group. PVF recordings demonstrated a significant increase in time velocity integrals of the S wave with both dobutamine (12.2 +/- 3.1 v 13.7 +/- 3.2 cm) and enoximone (11.0 +/- 3.0 v 12.2 +/- 3.2 cm). No changes in the systolic fraction of the PVF were noted. CONCLUSIONS There were no major differences in parameters reflecting diastolic function between the dobutamine- and the enoximone-treated groups.

Hemodynamic effects of the novel selective cAMP-phosphodiesterase III inhibitor R 80122 in anesthetized patients with moderate left ventricular dysfunction before coronary artery bypass grafting*

OBJECTIVE(S) To investigate the hemodynamic effects and safety of R 80122, a novel selective phosphodiesterase (PDE) III inhibitor, and its solvent hydroxypropyl-beta-cyclodextrin. DESIGN Prospective, randomized study. SETTING Operating theater of a university hospital in the Netherlands. PARTICIPANTS Twelve patients with impaired left ventricular function scheduled for coronary artery bypass grafting after induction of anesthesia were included. INTERVENTIONS R 80122 (n = 6) or its solvent (n = 6) was administered using the same infusion regimen. A bolus of 0.1 mL/kg (= 0.1 mg/kg R 80122) was infused over 10 minutes followed by a maintenance infusion of 5 microliters/kg/min (5 micrograms/kg/min R 80122) over 20 minutes. MEASUREMENTS AND MAIN RESULTS Compared with the solvent, patients receiving R 80122 did not show any significant changes in heart rate, arterial blood pressure, or pulmonary artery pressures. However, R 80122 produced a marked increase (P < 0.05) in cardiac output (thermodilution) and echocardiographically obtained percentage area reduction. No arrhythmias or ischemic episodes occurred during the infusion period. The plasma half-life of R 80122 was 10.6 +/- 1.9 minutes. CONCLUSIONS R 80122 appears to be a potent positive inotropic agent in these patients. Its use is not associated with marked vasodilation, it is devoid of positive chronotropic effects, and it can be administered safely in patients with impaired left ventricular function.

Perioperative Heart Failure

The incidence of perioperative heart failure is likely to increase as patient demographics are changing. More operations are performed on patients with increasing age and extensive cardiovascular disease.