Comparison of milrinone versus nitroglycerin, alone and in combination, on grafted internal mammary artery flow after cardiopulmonary bypass: effects of alpha-adrenergic stimulation.

OBJECTIVES: To compare changes in blood flow in a grafted internal mammary artery (IMA) after cardiopulmonary bypass (CPB) in response to the administration of milrinone or nitroglycerin and to establish the effects of alpha-adrenergic stimulation. DESIGN: Randomized study. SETTING: A university medical center hospital and a Veterans Affairs Medical Center hospital. PARTICIPANTS: Thirty consenting adults scheduled for elective coronary artery bypass graft surgery. INTERVENTIONS: Patients were randomized to receive a 2 microg/kg/min infusion of nitroglycerin (n = 10), a loading dose of 50 microg/kg of milrinone (n = 10), or both drugs combined (n = 10) shortly after CPB. Intravenous phenylephrine was administered to increase mean arterial pressure by 20%. IMA flow was measured with a calibrated laser Doppler flow probe. Hemodynamic and flow measurements were obtained before and after every intervention. MEASUREMENTS AND MAIN RESULTS: Nitroglycerin and milrinone increased mean IMA flow, but the increase was greater with milrinone. Both drugs combined were superior to nitroglycerin alone but not to milrinone. The addition of phenylephrine to nitroglycerin increased IMA flow in 6 of 10 patients. IMA flow decreased in 4 of 10 patients, however. Phenylephrine significantly increased IMA blood flow in patients receiving milrinone or in those given both drugs combined. CONCLUSION: After CPB, milrinone and nitroglycerin vasodilate the IMA; however, the combination of both drugs was not superior to milrinone alone. When using alpha-adrenergic stimulation, milrinone proved superior to nitroglycerin in preserving IMA flow.

Inhibition of phosphodiesterase type III before aortic cross-clamping preserves intramyocardial cyclic adenosine monophosphate during cardiopulmonary bypass.

UNLABELLED: Inotropes are often used to treat myocardial dysfunction shortly after cardiopulmonary bypass (CPB). beta-Adrenergic agonists improve contractility, in part by increasing cyclic adenosine monophosphate (cAMP) production, whereas phosphodiesterase type III inhibitors prevent its breakdown. CPB is associated with abnormalities at the beta-receptor level and diminished adenyl cyclase activity, both of which tend to decrease cAMP. These effects may be increased in the presence of preexisting myocardial dysfunction. We tested the hypothesis that inhibition of phosphodiesterase type III before global myocardial ischemia and pharmacologic arrest results in the preservation of intramyocardial cAMP concentration during CPB. Twenty adult patients undergoing coronary artery bypass grafting with CPB were studied. After CPB was instituted, a myocardial biopsy was obtained from the apex of the left ventricle. Patients were randomized to receive either placebo or milrinone (50 micro/kg) through the bypass pump 10 min before aortic cross-clamping. Another myocardial biopsy was performed adjacent to the left ventricular apex just before weaning from CPB. Myocardial cAMP concentration was determined by radioimmunoassay. Myocyte protein content was determined by the Bradford method by using a commercial kit. There were no significant demographic differences between the groups; however, patients in the Milrinone group had a lower left ventricular ejection fraction than placebo (41% +/- 13% vs 53% +/- 7%; P < 0.05). Patients who received milrinone had larger cAMP concentrations at the end of CPB compared with placebo (21 +/- 12.5 pmol/mg protein versus 12.8 +/- 2.2 pmol/mg protein; P < 0.05). The administration of milrinone before aortic cross-clamping is associated with increased intramyocardial cAMP concentration at the end of CPB. IMPLICATIONS: The administration of a single dose of milrinone before aortic cross-clamping resulted in significantly larger intramyocardial cyclic adenosine monophosphate concentration in myocardial biopsy specimens compared with controls.

Effects of calcium chloride on grafted internal mammary artery flow after cardiopulmonary bypass.

OBJECTIVE: To examine the effects of calcium chloride (CaCl2) administration on blood flow through the grafted left internal mammary artery (IMA) after cardiopulmonary bypass (CPB). DESIGN: Single-arm prospective study. SETTING: University-affiliated hospital operating room. PARTICIPANTS: Twenty adult patients scheduled for coronary artery bypass graft surgery with IMA graft. INTERVENTIONS: IMA flow was measured noninvasively with a laser Doppler flow probe placed around the IMA, and measurements were recorded for 10 seconds and averaged. After separation from CPB under stable hemodynamics, baseline IMA flow was measured. CaCl2, 15 mg/kg, was administered intravenously over 1 minute. Blood pressure, left atrial pressure, heart rate, and IMA flow were then measured at 1, 5, and 10 minutes. Coronary perfusion pressure and IMA vascular resistance were calculated. MEASUREMENTS AND MAIN RESULTS: After CaCl2 administration, IMA blood flow significantly decreased from baseline at 1, 5, and 10 minutes (from 28+/-9 mL/min to 19+/-8 mL/min, 22+/-6 mL/min, and 25+/-4 mL/min), with gradual return toward baseline over time. Blood pressure, coronary perfusion pressure, and IMA vascular resistance significantly increased at 1 and 5 minutes after CaCl2. Left atrial pressure and heart rate remained unchanged. No systolic regional wall motion abnormalities were detected on transesophageal echocardiography. CONCLUSIONS: CaCl2, administered as a bolus dose after separation from CPB, transiently but significantly reduces IMA flow and can potentially trigger vasospasm, increasing the risk for myocardial ischemia or infarction in susceptible patients. Further studies are needed to determine whether this effect also occurs with nitrosodilators or phosphodiesterase inhibitors.