Felipe Urdaneta

Respiratory complications in patients with traumatic cervical spine injuries: case report and review of the literature.

Spinal cord injuries continue to be a devastating medical problem. By impairing voluntary and involuntary nervous system function, virtually every body system function is affected. However, pulmonary function alteration and respiratory complications continue to be the major causes of morbidity and mortality in patients with spinal cord injuries. The current understanding of respiratory problems faced by patients with loss of innervation from cervical spinal cord injuries are reviewed.

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.

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

Inotropes are often used to treat myocardial dysfunction shortly after cardiopulmonary bypass (CPB). &bgr;-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 &bgr;-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 &mgr;g/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.

Treatment of ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in pigs, by sildenafil analogue (UK343-664) or nitroglycerin

In patients at risk for sudden ethanol (ETOH) intravascular absorption, prompt treatment of pulmonary hypertension (PHTN) will minimise the risk of cardiovascular decompensation. We investigated the haemodynamic effects of intravenous ETOH and the pulmonary vasodilatory effects of a sildenafil analogue (UK343-664) and nitroglycerin (NTG) during ETOH-induced PHTN in pigs. We studied pulmonary and systemic haemodynamics, and right ventricular rate or time derivate of pressure rise during ventricular contraction ( =dP/dT), as an index of contractility, in 23 pigs. ETOH was infused at a rate of 50 mg/kg/min, titrated to achieve a twofold increase in mean pulmonary arterial pressure (MPAP), and then discontinued. The animals were randomised to receive an infusion of 2 ml/kg ( n = 7) normal saline, a 500-microg/kg bolus of UK343-664 ( n = 8), or NTG 1 microg/kg ( n = 8); each was given over 60 seconds. Following ETOH infusion, dP/dT decreased central venous pressure (CVP), and MPAP increased significantly, resulting in significantly increased pulmonary vascular resistance (PVR). Within 2 minutes after treatment with either drug, CVP, heart rate (HR), and the systemic vascular resistance-to-pulmonary vascular resistance (SVR/PVR) ratio returned to baseline. However, at that time, only in the UK343-664 group, MPAP and dP/dT partially recovered and were different from the respective values at PHTN stage. NTG and UK343-664 decreased PVR within 2 minutes, from 1241+/-579 and 1224+/-494 dyne . cm/sec 5 , which were threefold-to-fourfold increased baseline values, to 672+/-308 and 538+/-203 dyne . cm/sec 5 respectively. However, only in the UK343-664 group, changes from baseline PVR values after treatment were significant compared to the maximal change during target PHTN. Neither drug caused a significant change in SVR. In this model of ETOH-induced PHTN, both UK343-664 and NTG were effective pulmonary vasodilators with a high degree of selectivity. However, the changes from baseline values of PVR, and the partial recovery of systemic pressure and RV contractility compared to the maximal change during target PHTN, were significant only in the sildenafil analogue group.

Effects of Sildenafil Analogue UK 343-664 on a Porcine Model of Acute Pulmonary Hypertension

BACKGROUND Sildenafil (Pfizer Pharmaceuticals, Sandwich, Kent, UK) has been associated with pulmonary vasorelaxation. A more potent Sildenafil analogue (UK 343-664 [Pfizer Pharmaceuticals]) has been developed, but its effects in vivo have not been studied. This study evaluated the effects of UK 343-664 (Pfizer) during acute pulmonary hypertension. METHODS Fourteen adult swine were anesthetized with 1 minimum alveolar concentration isoflurane and were mechanically ventilated with an FIO(2) of 50%. End tidal CO(2) was maintained between 32 and 36 mm Hg. Micromanometer tipped catheters were placed in the ascending aorta, pulmonary artery, and right ventricle. Pulmonary flow was measured with a perivascular probe using transit time ultrasound. RESULTS Pulmonary hypertension was induced with a continuous infusion of the thromboxane analogue U46619. Animals were randomized into two groups. Group 1 (n = 9) received 500 microg of UK 343-664 (Pfizer) intravenously for more than 2 minutes. Group 2 (n = 5) served as the control group. Data were recorded continuously for 60 minutes. Statistical analyses were performed with the analysis of variance and t tests. A p less than 0.05 was considered significant.Pulmonary hypertension was achieved in all animals. The administration of UK 343-664 (Pfizer) was associated with a significant decrease in pulmonary artery pressure (30.3%; p < 0.05) and pulmonary vascular resistance (42%; p < 0.05) with mild systemic vasodilatation. These effects were partially maintained at 30 minutes (a 17.3% and 39% decrease, respectively; p < 0.05). CONCLUSIONS The administration of UK 343-664 (Pfizer) was associated with predominant pulmonary vasodilatation without systemic hypotension. This may represent a significant advance in the treatment of acute pulmonary hypertension. Potential clinical implications for this new phosphodiesterase enzyme type V (PDEV) inhibitor merit further study.

Noncardiogenic pulmonary edema and rhabdomyolysis after protamine administration in a patient with unrecognized Mcardle's disease

Noncardiogenic Pulmonary Edema and Rhabdomyolysis after Protamine Administration in a Patient with Unrecognized McArdles Disease Emilio Lobato;Gregory Janelle;Felipe Urdaneta;Mark Malias; Anesthesiology

Treating myocardial stunning randomly, with either propofol or isoflurane following transient coronary occlusion and reperfusion in pigs.

Propofol and isoflurane may be used during fast track anesthesia for off-pump bypass, where transient ischemia is common. The purpose of this study was to compare the effects of propofol vs isoflurane in a porcine model of acute coronary occlusion. Twenty five pigs were randomized to receive general anesthesia with either isoflurane, 1 MAC (n = 13), or propofol, 3 mg/kg bolus followed by 200 microg/ kg/min infusion (n = 12). Pressure-tipped catheters were placed in the left ventricle (LV) and carotid artery; cardiac output was measured by ultrasound; two pairs of ultrasonic dimension catheters were placed in the subendocardium of LV. The slope of LV end-systolic pressure-volume relationship (Emax) was calculated. Reversible ischemia for 15 mins was accomplished with an occluder around the left anterior descending artery followed by reperfusion period. Measurements were done at baseline, end ischemia, early (5 min) and late (30 min) reperfusion. The data collected included systemic hemodynamics, LV end-diastolic pressure (LVEDP), dP/dt, Emax, and the presence of ventricular arrhythmias. The number of animals studied to completion was 19 (n = 11 in the isoflurane group; n = 8 in propofol group). There was a significant difference in Emax between isoflurane and propofol during early and late reperfusion [3.4 (0.5) and 4.0 (0.3) vs 2.6 (0.4) and 3.2 (0.5) mmHg/sec, respectively; P < 0.05]. Postreperfusion ventricular fibrillation occurred in 54% animals in the propofol group vs none in the isoflurane group ( P 0.05). Isoflurane administration was found to be cardioprotective against ventricular depression and arrhythmias compared to propofol.

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 μg/kg; sildenafil-analog (n=5) 500 μg/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.

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.