Treating pulmonary hypertension post cardiopulmonary bypass in pigs: milrinone vs. sildenafil analog.

Procedures using cardiopulmonary bypass (CPB) and aortic cross-clamping are associated with a variable degree of ischemia/reperfusion of the lungs, leading to acute pulmonary hypertension (PHT). The purpose of this study was to compare the effects of the sildenafil analog (UK343-664), a phosphodiesterase type V(PDEV) inhibitor, with milrinone, a PDE type III inhibitor, in a porcine model of acute PHT following CPB. After the pigs were anesthetized, pressure-tipped catheters were placed in the right ventricle and carotid and pulmonary arteries. Cardiac output was measured with an ultrasound probe on the ascending aorta. After heparinization and placement of aortic and right atrial cannulae, non-pulsatile CPB was instituted and cardioplegia administered following aortic cross-clamping. After 30 minutes, the clamp was removed and the animals re-warmed and separated from CPB in sinus rhythm. The animals were randomized to 3 groups, and 16 animals were studied to completion: milrinone (n=5) 50 microg/kg; sildenafil-analog (n=5) 500 microg/kg; and normal saline (NS) (n=6). Hemodynamic data were collected at baseline pre-CPB and, following termination of CPB, at baseline, 5, 10 and 30 minutes after administration of the drug. Pulmonary hypertension was present in all groups following CPB. After administration of the drugs, mean pulmonary artery pressure decreased in all 3 groups; however, only in the sildenafil-analog group did pulmonary vascular resistance(PVR) decrease by 35%, from 820 to 433 dynes . cm . sec(-5) at 5 minutes (p<0.05), and continued to be decreased at 10 minutes by 26% (P<0.05). Pulmonary selectivity was demonstrated with sildenafil-analog, because there were no similar changes in systemic vascular resistance(SVR) and no significant changes in systemic hemodynamics. Sildenafil-analog, a PDEV inhibitor, shows a promising role for managing the PVR increases that occur following CPB.

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.

[Viral agents in patients with infectious processes of the central nervous system]. / Agentes virales en pacientes con procesos infecciosos del Sistema Nervioso Central.

Local statistics report a great number of cases of neurological diseases of unidentified cause. The purpose of this research was to determine the presence of viral agents in patients with affection of the central nervous system, in Zulia State, Venezuela. In different health centers throughout the state, we collected 129 randomized samples of cerebrospinal fluid (CSF) and serum from patients ranging from 1 day to 41 years of age, showing symptoms of CNS disease and whose bacteriological test resulted negative. The serum/CSF albumin ratio was determined to exclude contaminated CSF samples, thus 54 optimal samples were obtained for the research. We determined serum IgM and CSF IgG specific for Venezuelan equine encephalomyelitis (VEE), Herpes simplex (HSV), Epstein Barr (EBV), Dengue, Rubella and Measles virus, through ELISA and indirect immunofluorescence techniques. Of the 54 samples studied, 33 (61.11%) were positive. %). The etiological agents implicated were VEE 14 cases (42.42%); HSV 11 cases (33.33%); EBV 5 cases (15.15%) and Dengue 3 cases (9.09%). We did not detect Rubella o Measles. Regarding the age distribution, the most affected group was that of children under 12 (83.34%). We analyzed the clinical manifestations and the CSF characteristics and did not find differences suggestive of an specific etiological diagnosis, even though certain signs could be considered early indications of CNS alterations due to viral causes. Our study shows that a large percentage of CNS affections of unknown etiology are produced by viral agents, indicating that in our region, most of this cases are not registered.

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.

Effects of milrinone versus epinephrine on grafted internal mammary artery flow after cardiopulmonary bypass.

OBJECTIVE: To compare changes on grafted internal mammary artery (IMA) flow after cardiopulmonary bypass in response to the administration of milrinone or epinephrine. DESIGN: Prospective and randomized. SETTING: University-affiliated hospital. PARTICIPANTS: Twenty consenting, adult patients undergoing CABG. INTERVENTIONS: Patients were randomized to receive either milrinone, 50 microg/kg, or epinephrine, 0.03 microg/kg/min, immediately after cardiopulmonary bypass. IMA flow was measured with a laser Doppler flow probe before and after the administration of either drug. MEASUREMENTS AND MAIN RESULTS: Baseline grafted IMA flow was similar for both groups (milrinone, 38+/-14 mL/min; epinephrine, 33+/-10 mL/min). In patients who received milrinone, flow increased by 24% to 50+/-17 mL/min, p<0.05; whereas with epinephrine, it remained essentially unchanged (33+/-10 v. 31+/-11 mL/min). CONCLUSIONS: This study confirms that the vasodilatory effect of milrinone on the IMA is also present after its anastomosis, whereas low-dose epinephrine exhibits neither beneficial nor adverse effects. It is suggested that in the absence of excessive vasodilation, milrinone should be considered as a first-line inotrope after coronary artery bypass graft surgery, to achieve an increase in contractility and IMA artery flow.

Noncardiogenic pulmonary edema associated with protamine administration during coronary artery bypass graft surgery.

Protamine sulfate is the only agent approved to reverse heparin-induced anticoagulation. As with any other drug, protamine has the potential to cause adverse effects that range from mild hypotension to potentially fatal events, such as noncardiogenic pulmonary edema (NCPE) and catastrophic pulmonary vasoconstriction. We report a case of NCPE after the administration of protamine to a patient undergoing coronary artery bypass graft surgery and discuss the diagnosis and management of this severe adverse event.