Dennis D. O'Keefe

Transfusion of Predonated Autologous Blood in Elective Cardiac Surgery

Despite blood conservation techniques, the average transfusion requirement in patients undergoing elective cardiac surgical procedures remains 1 to 3 units. We studied the efficacy of predonated autologous blood in decreasing homologous transfusion in two matched groups of 58 patients each. Group 1 received homologous blood perioperatively, and Group 2 was transfused with predonated autologous blood. An average of 1.97 units was predonated in Group 2 over 18 days. This resulted in a decline in whole blood hemoglobin concentration of 2.2 gm/dl. No complications resulted from phlebotomy in this ambulatory population consisting predominantly of patients with coronary artery disease. Transfusion of an average of 1.7 units of autologous blood in Group 2 reduced the volume of homologous transfusion by 46% compared with Group 1 (p less than .01). In Group 1, 38% of patients required no homologous transfusion compared with 64% in Group 2 (p less than .02). There were no complications related to autologous blood transfusion. Total transfusion requirement was related to the length of cardiopulmonary bypass. We conclude that autologous predonation is a simple, safe, and cost-effective method of reducing homologous transfusion and thereby decreasing the risk of transfusion-related reactions and infections.

Relation between ionized calcium concentration and ventricular pump performance in the dog under hemodynamically controlled conditions

The effect of plasma ionized calcium concentration on left ventricular function was studied in the canine heart on right heart bypass. Stroke volume, mean arterial pressure and heart rate were controlled. Plasma ionized calcium was lowered to 0.58 +/- 0.01 mM by citrate infusion and raised to 1.70 +/- 0.01 mM by calcium chloride infusion in random order in each dog. Left ventricular function at each of these ionized calcium levels was compared with that in an immediately preceding normocalcemic period. At a constant stroke work (16.9 +/- 0.2 g-m), sustained hypercalcemia was associated with a small decrease in left ventricular end-diastolic pressure (1.7 +/- 0.7 cm H2O, p less than 0.05) despite a marked increase in peak left ventricular dP/dt (first derivative of ventricular pressure) averaging 34 percent (p less than 0.001). Coronary blood flow, tension-time index and myocardial oxygen consumption were not significantly altered. Stroke work determined at a left ventricular end-diastolic pressure of 14 cm H2O, by interpolation in left ventricular function curves, was 11 +/- 4.4 percent above that at control normocalcemia (p less than 0.05). At a constant stroke work (16.9 +/- 0.2 g-m), sustained hypocalcemia was associated with a marked depression of left ventricular function as demonstrated by a substantial increase (from 4.9 +/- 0.3 to 12.7 +/- 1.1 cm H2O, p less than 0.0001) in left ventricular end-diastolic pressure (p less than 0.0001), decreased mean systolic ejection rate (p less than 0.01) and decreased peak left ventricular dP/dt (p less than 0.0001). Coronary blood flow increased (p less than 0.05) whereas myocardial oxygen consumption did not change significantly. A marked displacement of left ventricular function curves to the right (compared with curves obtained during normocalcemia) was observed, and stroke work determined at a left ventricular end-diastolic pressure of 14 cm H2O was 52 +/- 5.4 percent below control level (p less than 0.001). It appears that hypercalcemia, when initiated from a normal control level, provides only a small enhancement of ventricular pump performance (as indexed by the stroke work-left ventricular end-diastolic pressure relation) despite a marked increase in peak left ventricular dP/dt, whereas marked improvement of left ventricular performance may be expected when calcium infusion is initiated from an ionized calcium level that is below normal.

The Superiority of Cold Oxygenated Dilute Blood Cardioplegia

It has been clearly shown, both in a laboratory model and in humans, that oxygenation of crystalloid cardioplegic solutions markedly enhances myocardial preservation. The addition of a small volume of red cells to a crystalloid perfusate improves capillary perfusion. Based on these results, we have changed our cardioplegic solution from cold crystalloid to cold oxygenated dilute blood. In the present study we retrospectively evaluate the results of 400 operative procedures to determine whether the addition of oxygenation and a small volume of blood to the cardioplegic solution enhances myocardial protection in the clinical setting. Two hundred consecutive patients who underwent operation with cardioplegic arrest using a cold crystalloid cardioplegic solution (group 1) were compared with a subsequent 200 patients who underwent operation with cold oxygenated dilute blood cardioplegia (group 2). Patients in group 2, who received cold oxygenated dilute blood cardioplegia, had a significantly reduced need for postoperative intraaortic balloon pump counterpulsation and for atrioventricular pacing. Also, patients in group 2 had a lower incidence of perioperative myocardial infarction and had improved early outcome. None of the 200 patients in group 2 had electrocardiographic evidence of perioperative infarction. We conclude that cold oxygenated dilute blood cardioplegia provides better preservation than does a nonoxygenated crystalloid solution during elective ischemic arrest, because a cold crystalloid solution is able to deliver oxygen and the red cells are able to enhance capillary perfusion.

Myocardial preservation related to magnesium content of hyperkalemic cardioplegic solutions at 8 °C

Abstract This study investigates whether the addition of magnesium to a hyperkalemic cardioplegic solution containing 0.1 mM ionized calcium improves myocardial preservation, and whether there is an optimal magnesium concentration in this solution. Isolated perfused rat hearts were arrested for two hours by this cardioplegic solution, which was fully oxygenated and infused at 8 °C every 15 minutes to simulate clinical conditions. The cardioplegic solution contained either 0, 2, 4, 8, 16, or 32 mM magnesium. At end-arrest, the myocardial creatine phosphate concentration (nanomoles per milligram of dry weight) was 20.7 ± 2.1, 22.9 ± 1.7, 24.8 ± 2.0, 31.3 ± 1.4, 33.1 ± 1.8, and 31.6 ± 0.8, respectively, in hearts given cardioplegic solution containing these magnesium concentrations. Thus, the concentration of creatine phosphate was significantly higher at end-arrest when the cardioplegic solution contained 8, 16, or 32 mM than 0 or 2 mM magnesium ( p p p

Relation of myocardial protection to cardioplegic solution pH: Modulation by calcium and magnesium

The relationship between myocardial preservation and cardioplegic solution pH was assessed in isolated, perfused rat hearts. A base solution without calcium or magnesium and the same solution containing 0.2 mmol/L ionized calcium or 16 mmol/L magnesium or both ions were studied at several values of pH between 6.8 and 8.7. Hearts were arrested at 8 degrees C by multidose infusions of these bicarbonate-buffered solutions bubbled with oxygen and a varying percentage of carbon dioxide to control pH. Diastolic tone (left ventricular balloon) and adenosine triphosphate (ATP) depletion during arrest both increased as the cardioplegic solution became more alkaline. Calcium increased these effects of pH. Magnesium weakened the effect of pH on diastolic tone, maintained ATP at all pH levels, and inhibited the effects of calcium on the relationships of pH to diastolic tone and ATP. When data from all solutions were considered together, ATP depletion was shown to be linearly related to diastolic tone. Calcium depressed functional recovery (left ventricular developed pressure during reperfusion expressed as a percentage of its prearrest value) at all pH levels. With the other solutions, recovery was similar and best within a broad and relatively alkaline pH range. With the solution containing calcium and magnesium, at pH levels of 8.28 +/- 0.02, 7.87 +/- 0.03, 7.58 +/- 0.02, 7.41 +/- 0.01, 7.06 +/- 0.02, and 6.80 +/- 0.01, recovery at 5 minutes of reperfusion was 101.4% +/- 3.7%, 102.9% +/- 2.8%, 107.3% +/- 3.7%, 102.8% +/- 2.9%, 91.8% +/- 3.6%, and 94.3% +/- 3.5%, respectively. This effect of alkalinity was short-lived. Extreme alkalinity of the base, acalcemic solution produced the calcium paradox, as reported previously. Good preservation of ATP by the most acid solutions did not predict good functional recovery. Magnesium increased the persistence of frequent extrasystoles during early reperfusion, but the effect was attenuated by calcium. The data support the inclusion of magnesium in cardioplegic solutions, particularly when they contain calcium, show that cardioplegic solution pH can have major effects on the arrested heart, and suggest that a relatively alkaline pH may modestly benefit functional recovery.

Protection of the hypertrophied myocardium by crystalloid cardioplegia.

Patients with left ventricular hypertrophy (LVH) have a worse outcome after cardiac surgery than those without hypertrophy. We studied protection of hearts with LVH in an isolated rat heart model using multidose, cold, oxygenated cardioplegia. LVH was produced by banding the abdominal aorta in young rats. Six weeks after banding, this produced a 31% increase in the left ventricular dry weight/body weight ratio compared to two age-matched control groups comprising sham-operated and nonoperated animals. The recovery of cardiac output after arrest was higher in LVH (82 +/- 4% of prearrest) than in sham-operated (69 +/- 4%) or nonoperated (66 +/- 3%) control groups. The improved functional recovery in LVH occurred although there were no differences among the groups in myocardial adenosine triphosphate (ATP) and phosphocreatine (PCr) prior to arrest, at the end of arrest, or after reperfusion. Glycogen levels were also similar among the three groups prior to arrest and after reperfusion but were highest in LVH after arrest. Myocardial oxygen consumption (MVO2) and efficiency, expressed as cardiac output/MVO2, were similar among the groups prior to arrest. Myocardial efficiency after reperfusion declined in all groups but was best preserved in LVH. We also compared the sensitivity of hypertrophied and control hearts to the deleterious effects of calcium in cardioplegia. Calcium in the cardioplegia increased myocardial lactate production during arrest in a dose-related fashion and depressed myocardial levels of ATP, PCr, and glycogen at end arrest in all groups. Cardiac output recovery was also depressed by calcium but was still best in LVH. We conclude that the hypertrophied myocardium is well protected by standard cardioplegia and that calcium in cardioplegia does not preferentially depress recovery in LVH.

Maximal Oxygenation of Dilute Blood Cardioplegic Solution

Abstract The content of dissolved O 2 (the major source of O 2 far the myocardium) of dilute blood cardioplegic solution (dBCS) varied widely when oxygenated at 4 °C by surface flow of O 2 in a Bentley BCR-3500 cardiotomy reservoir. We have modified the system to consistently deliver maximally oxygenated dBCS to the heart. Laboratory studies indicated that bubbling O 2 through a 16-gauge intravenous catheter in a central Luer-Lok port of the cardiotomy reservoir provided contents of dissolved O 2 that were consistently near maximal. We then studied 17 patients in the operating room. The first 6 patients received dBCS oxygenated with 100% O 2 with a high dissolved O 2 content of 3.2 ± 0.2 ml/dl. However, the pH of the dBCS became highly alkaline (7.83 ± 0.11 at 37 °C). Therefore, in the remaining 11 patients, 2% CO 2 was added to the O 2 . The dissolved O 2 content remained high (3.3 ± 0.1 ml/dl), and the pH was in a more physiological range (7.35 ± 0.09 at 37 °C). We conclude that consistently maximal oxygenation of a dBCS at a more physiological pH can be achieved by this method.

Effects of continuous nitroglycerin infusion on acute myocardial ischemia in dogs

Abstract The effects of a continuous infusion of nitroglycerin (NTG) were evaluated by hemodynamic measurements and measurements of regional myocardial blood flow (RMBF) in dogs on right heart bypass with left anterior descending coronary artery ligation. NTG infusion which decreased afterload, mean aortic pressure (MAP) decreased from 100 to 85 mm Hg, thus also decreasing coronary perfusion pressure) resulted in an 11.8% increase in total coronary blood flow (CBF), a 19.1% decrease in coronary vascular resistance index (CVRI), and a 21.7% decrease in myocardial oxygen consumption (MVO 2 ). When MAP was returned to the control level (100 mm Hg) with continuing infusion of NTG, CBF increased 49.1%, and CVRI decreased by 23.4% compared to the pre-NTG ischemic state. Regional myocardial blood flow (microsphere technique) to ischemic tissue at the border of the infarct remained stable with NTG infusion despite decreased MAP, in contrast to the significant fall in RMBF in this region with decreased MAP in the control group without NTG. When MAP was elevated back to pre-NTG levels, an 18.6% increase in RMBF to the border of the infarct was seen compared to an insignificant change in RMBF in untreated (control) animals. These data are consistent with the concept that under conditions of regional myocardial ischemia, coronary blood flow to the “border zone” (ischemic myocardium) is maintained or enhanced by NTG, even when coronary perfusion pressure is modestly reduced.

Myocardial oxygen consumption with isoproterenol versus calcium chloride in hypocalcemic ventricular failure in dogs

In 30 dogs on right heart bypass we compared the effects of isoproterenol with those of calcium chloride on myocardial oxygen consumption and on left ventricular function in the setting of ventricular depression produced by ionized hypocalcemia. In 22 dogs (Groups A and B) either isoproterenol or calcium chloride was infused, left ventricular function curves were generated, and end-diastolic pressure vs segment length plots were obtained. In 8 dogs (Group C), with initial hypocalcemia, both isoproterenol and calcium chloride were infused separately in random order to produce an equal decrease in left ventricular end-diastolic pressure at constant mean aortic pressure, heart rate, and cardiac output. Myocardial oxygen consumption and indices of left ventricular function were obtained. In Groups A and B, both drugs, when administered to the ventricle depressed by hypocalcemia, displaced left ventricular function curves upward and to the left. Left ventricular stroke work at constant left ventricular end-diastolic pressure increased (from 13.0 +/- 1.3 to 31.2 +/- 2.3 g X m for isoproterenol; from 13.9 +/- 2.5 to 32.5 +/- 2.5 g X m for calcium chloride). In Group C, there were no significant differences between left ventricular end-diastolic pressure, end-diastolic internal diameter, myocardial oxygen consumption, or peak left ventricular dP/dt in the hypocalcemic periods preceding isoproterenol and calcium chloride infusion. When the two drugs caused matched decreases in left ventricular end-diastolic pressure (-7.4 +/- 0.5 cm H2O for isoproterenol; -7.3 +/- 0.8 cm H2O for calcium chloride) there were similar decreases in end-diastolic internal diameter. However, isoproterenol was associated with a significantly greater (P less than 0.001) myocardial oxygen consumption (13.7 +/- 0.4 ml X 100 g-1 X min-1) than calcium chloride infusion (11.9 +/- 0.4 ml X 100 g-1 X min-1), as well as a greater peak left ventricular dP/dt (P less than 0.005).

Regional Myocardial Protection during Aortic Cross-clamp Ischemia in Dogs: Calcium-Containing Crystalloid Solutions

To study the effects of calcium in cardioplegic solutions, an in situ dog heart model was used that allowed infusion of two different cardioplegic solutions into separate regions of the same heart. Two concentrations of ionized calcium, 1.0 mM and 0.5 mM, in a cold, potassium-containing solution were tested in two groups of dogs and compared with the same cold, potassium-containing solution but without the calcium, during 100 minutes of global myocardial ischemia induced by aortic clamping. Results were evaluated in terms of percent change of regional systolic shortening measured with ultrasonic piezoelectric crystals, percent change of regional myocardial blood flow, and change of regional left ventricular myocardial diastolic distensibility. No significant differences were found between myocardial regions protected with calcium of either concentration and regions protected with calcium of either concentration and regions protected without calcium. This study could demonstrate no beneficial or adverse effects of including calcium in this type of crystalloid cardioplegic solution applied to an in situ dog heart model.