Effect of preload on ischaemic and non-ischaemic left ventricular regional function.

The response to preload of ischaemic and non-ischaemic regions of the left ventricle was studied in 14 dogs undergoing right heart bypass with mean aortic pressure and heart rate held constant. Regional function was measured by sonomicrometry before and after coronary artery occlusion. In the ischaemic region, as expected, there was paradoxical systolic lengthening (that is, systolic shortening was negative) but as stroke volume was progressively increased end diastolic length increased, whereas end systolic length changed little; thus systolic lengthening decreased (systolic shortening increased). Ischaemic regions that were dyskinetic at low stroke volumes were virtually akinetic at high stroke volumes. Additional studies showed that this response was not attributable to increased regional blood flow at high preloads and occurred over a wide range of heart rates and mean aortic pressures. Plots of systolic shortening against end diastolic length, expressing the regional Frank-Starling relation, were well described by linear regression in both ischaemic and non-ischaemic regions, although a few of these relations were better described by higher order polynomials. The slopes of these relations in the ischaemic region were 0.86(0.05) before and 0.83(0.06) after ligation, reflecting a small effect of preload on end systolic length. The data suggest that when contractility and afterload are constant preload determines the magnitude and in certain instances the sign of systolic shortening. In any ischaemic regions incapable of developing force the positive slope of the Frank-Starling relation is attributable to myocardial passive elastic properties. Paradoxical lengthening does not, however, necessarily indicate the absence of active force development; positive and negative values of systolic shortening describe a continuous spectrum of regional contractility. Thus the effects of preload and contractility on systolic shortening in ischaemic as well as non-ischaemic myocardium require differentiation.

Effects of insulin, tolbutamide, and glucagon on activities of jejunal carbohydrate-metabolizing enzymes in humans.

The activities of jejunal carbohydrate-metabolizing enzymes show adaptive drugs, and sex hormones. To learn whether insulin, tolbutamide, and glucagon had effects on these enzymes, we performed serial peroral jejunal biopsies in normal young men and in obese patients, before and after treatment with these agents. Jejunal mucosa was assayed for glycolytic enzyme activities, pyruvate kinase (PK), hexokinase (HK), and fructose-1,6-diphosphate aldolase (FDPA), and the nonglycolytic enzyme activity, fructose diphosphatase (FDPase). Insulin significantly increased the activity of jejunal PK (+48% change from control) and HK (+6%), decreased the activity of FDPase (-36%),and had no effect on FDPA. Glucagon had opposite effects; the activity of PK was decreased (-33%) and FDPase was increased (+50%). Tolbutamide significantly increased the activities of PK (+47%), HK (+14%), and FDPA (+7%), and decreased the activities of FDPase (-36%). The results of tolbutamide on glycolytic enzyme activities were independent of endogenous insulin. The data support the concept that jejunal carbohydrate-metabolizing enzymes in man respond to hormones and drugs similar to responses observed in rat liver. This is important because it now gives us a means of studying the actions of these hormones directly in human tissue.

Prediction of outcome in acute renal failure.

In an attempt to predict outcome in acute renal failure (ARF) we have utilized multiple logistic regression to analyze clinical data from 151 patients with ARF seen over a 15-month period. Recovery of renal function occurred in 60% of patients with a 58% survival. Our analysis demonstrated sepsis, respiratory failure, and oliguria to be the major predictors of nonrecovery of renal function. A logistic equation was generated for prediction of outcome and was validated in a second independent group of patients with ARF. Prediction of outcome could be achieved with a sensitivity of 75% and a specificity of 80%. Maximum sensitivity (100%) was associated with a 17% specificity, while maximum specificity (98%) yielded a sensitivity of 20%.

Diazepam-fentanyl interaction--hemodynamic and hormonal effects in coronary artery surgery.

Diazepam has been reported to produce hypotension when administered with anesthetic doses of fentanyl. Twenty patients undergoing coronary bypass surgery were randomly assigned to one of four treatment groups: group 1, no diazepam; groups 2, 3, and 4, 0.125, 0.25, and 0.5 mg X kg -1 of diazepam, respectively. All patients then received 50 micrograms X kg -1 fentanyl at 400 micrograms X min -1 and 0.4 mg X kg -1 metocurine at 2 mg X min -1. Hemodynamic parameters were recorded and blood was sampled for measurement of plasma catecholamine and histamine concentrations. Heart rate, cardiac index, stroke volume index, central venous pressure, pulmonary arterial and wedge pressures, and pulmonary vascular resistance did not change significantly in any group. Patients in groups 2-4 had significant decreases in mean arterial pressure and systemic vascular resistance during fentanyl infusion. These hemodynamic changes were accompanied by decreases in plasma epinephrine and norepinephrine levels. These hemodynamic and hormonal changes did not occur in patients given fentanyl only. Plasma histamine levels did not change significantly in any group. Caution should be used when diazepam in doses as small as 0.125 mg X kg -1 are combined with high-dose fentanyl anesthesia.

Comparative cardiovascular effects of midazolam and thiopental in healthy patients.

Midazolam, a water-soluble benzodiazepine that is shorter-acting, more potent, and less irritating to veins than diazepam, has been suggested for use for induction of anesthesia. The cardiovascular effects of an induction-sized dose (0.25 mg/kg) of midazolam in A.S.A. class I or II surgical patients (N = 11) sedated with morphine and N2O-O2 were compared in a double-blind fashion with a similar group of patients (N = 9) receiving thiopental (4.0 mg/kg). Consistent with earlier studies, patients given thiopental experienced downward trends from base line in mean arterial pressure, stroke volume, cardiac output, and heart rate; mean right atrial pressure increased slightly, whereas systemic vascular resistance did not change. Induction of anesthesia with midazolam was associated with more gradual and less pronounced hemodynamic alteration; the only significant changes from base line were decreases in mean arterial pressure 5 and 10 minutes after injection. When the two groups were compared, no significant differences were found. Midazolam is, then, as acceptable for induction of anesthesia as thiopental from a hemodynamic point of view in A.S.A. class I and II patients.

Cardiovascular effects of midazolam and thiopentone for induction of anaesthesia in ill surgical patients.

The cardiovascular effects of midazolam (0.15 mg kg-1) and thiopentone (3.0 mg kg-1) were compared during induction of anaesthesia in 20 American Society of Anesthesiologists class III patients. In patients given thiopentone (N = 11), cardiac output, mean arterial pressure, heart rate, and systemic vascular resistance all decreased significantly over the course of the study period; mean right atrial pressure rose slightly, and stroke volume remained the same. Patients receiving midazolam (N = 9) experienced similar haemodynamic changes which were significant relative to baseline only for the fall in mean arterial pressure and the rise in mean right atrial pressure at ten minutes. There were no significant differences between the two groups. Midazolam thus appears to be at least as acceptable an induction agent as thiopentone in ill patients, from a haemodynamic point of view.

Reduction of postischemic myocardial dysfunction by substrate repletion during reperfusion.

We studied the effect of selected metabolic substrates on recovery of myocardial function and ATP concentration when added to the reperfusate after normothermic ischemia. The hearts of 30 anesthetized, open-chest mongrel dogs were subjected to 45 min of global ischemia at 37 degrees C followed by 90 min of reperfusion. Left ventricular function curves were generated on right heart bypass before and at 30 min intervals after the ischemic period. ATP concentration was measured before, at the end of, and 90 min after the ischemic period. Experiments were randomized into five groups distinguished by the content of the myocardial reperfusate during the first 10 min of the reperfusion period. Hearts received either unmodified oxygenated pump blood (control; group I), normothermic oxygenated 28 mmol/liter potassium-blood cardioplegic solution (KBC; group II), 25 mmol/liter glutamate in KBC (group III), 250 mumol/liter adenosine with 1 mg erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride (EHNA) and glutamate in KBC (group IV), or 2 mmol/liter ribose and glutamate (group V) in KBC. Hearts reperfused with KBC showed improvement early (group II vs group I; p less than .02) but not late recovery of left ventricular function over control. Glutamate, which replenishes Krebs cycle intermediates lost during ischemia, increased functional recovery (group III vs group II; p less than .002). Ribose, which is important in purine salvage and resynthesis, added to glutamate-KBC further improved functional recovery (group V vs group III; p less than .01). Adenosine, a precursor of ATP, with EHNA, an inhibitor of rapid adenosine catabolism, added to glutamate-KBC depressed early recovery (group IV vs group III; p less than .01); however, recovery improved with time. Both glutamate and ribose with glutamate in KBC improved ATP recovery (groups III and V vs group II; p less than .002). Thus selective substrate repletion during initial reperfusion after severe normothermic ischemia can improve recovery of myocardial function and ATP concentration.

Myocardial recovery after hypothermic arrest: a comparison of oxygenated crystalloid to blood cardioplegia. The role of calcium.

We compared multidose crystalloid hyperkalemic cardioplegic solutions with and without added red cells in 24 canine hearts subjected to 5 hr of arrest at 10 degrees C. All cardioplegic solutions were fully oxygenated at 4 degrees C before delivery. Since blood cardioplegia contained Ca++ carried over with the red cells, Ca++ was added to the crystalloid solution in one group. The table below shows the hematocrit (HCT) and ionized Ca++ concentrations of the cardioplegic solutions, and coronary arteriovenous oxygen difference during infusion of cardioplegic solution (AVO2) (ml O2/100 ml). Recovery during reperfusion is shown as percent of prearrest left ventricular function (LVF) and prearrest myocardial ATP concentration.

Warm and cold blood cardioplegia. Comparison of myocardial function and metabolism using 31p magnetic resonance spectroscopy.

BACKGROUND: Standard myocardial protection during cardiac surgery uses hypothermic arrest, but warm heart surgery, recently introduced, is now used in many centers. We hypothesized that warm continuous blood cardioplegia (WCBC) would provide better myocardial preservation than cold continuous blood cardioplegia (CCBC). METHODS AND RESULTS: In isolated cross-perfused canine hearts, left ventricular (LV) function and myocardial O2 consumption (MVO2) were measured at constant LV volume, coronary perfusion pressure, and heart rate before and after 75 minutes of arrest at 37 degrees C or 10 degrees C. Metabolism was evaluated by 31P nuclear magnetic resonance spectroscopy. LV resting tone increased transiently after arrest by CCBC but not WCBC (38 +/- 3.9 versus 2.9 +/- 0.5 mm Hg, P < .0005). Myocardial ATP changed over time differently in the groups (P < .001), declining at the outset of CCBC and returning to control levels during the recovery period after CCBC or WCBC. Intracellular pH rose from 7.17 +/- 0.03 to 7.85 +/- 0.05 during CCBC (P < .0005 versus WCBC). MVO2 declined dramatically during arrest at either temperature but to a lower value during CCBC (P < .0005). LV pressure recovered to 86.1 +/- 5.1% of its prearrest value after CCBC and to 97.2 +/- 7.8% following WCBC (P = NS). After CCBC but not WCBC, there were small but significant increases in LV end-diastolic pressure (by 1.3 mm Hg, P < .05) and in the LV relaxation constant, tau (from 37.3 +/- 1.5 to 42.3 +/- 2.4 milliseconds, P < .05). CONCLUSIONS: The increase in intracellular pH during CCBC is largely accounted for by physicochemical factors. Group differences in ATP over time may be related to rapid cooling contracture during CCBC. The data suggest that CCBC mildly impairs LV function but that WCBC preserves function and metabolism at or near prearrest levels.