Chemical profiling by UHPLC-Q-TOF-HRESI-MS/MS and antibacterial properties of Entada abyssinica (Fabaceae) constituents.

A rapid untargeted UHPLC-Q-TOF-ESI-MS/MS-Based metabolomic profiling of the medicinal plant Entada abyssinica was performed. A total of 18 metabolites were detected, of which 10 could not be identified. Based on this result, an extensive chemical investigation of the CH2Cl2-MeOH (1:1) extract of this plant was carried out, leading to the isolation of a new ceramide, named entadamide (1), together with nine known compounds: monomethyl kolavate (2), 24-hydroxytormentic acid (3) chondrillasterol (4), 3-O-ß-D glucopyranosylstigmasterol (5), 3-O-ß-D glucopyranosylsitosterol (6), quercetin 3'-methylether (7), 2,3-dihydroxypropyl icosanoate (8), 2,3-dihydroxy-propyl 23-hydroxytricosanoate (9) and 2,3-dihydroxy-propyl 24-hydroxytetracosanoate (10). Their structures were elucidated by the analyses of their spectroscopic and spectrometric data (1D and 2D NMR, and HRESI-MS) in comparison with those reported in the literature. Furthermore, the crude extract and some isolated compounds were tested against non-ciprofloxacin resistant strains viz, Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922), Samonella thyphi (ATCC 19430) and Samonella enterica (NR4294). The tested samples demonstrated significant activity against all the tested bacteria (MIC values: 3.12-12.5 µg/mL).

Cardiogenic shock due to acute severe mitral regurgitation complicating acute myocardial infarction: a report from the SHOCK Trial Registry. SHould we use emergently revascularize Occluded Coronaries in cardiogenic shocK?

OBJECTIVES: Our objective was to define the outcomes of patients with cardiogenic shock (CS) due to severe mitral regurgitation (MR) complicating acute myocardial infarction (AMI). BACKGROUND: Methods for early identification and optimal treatment of such patients have not been defined. METHODS: The SHOCK Trial Registry enrolled 1,190 patients with CS complicating AMI. We compared 1) the cohort with severe mitral regurgitation (MR, n = 98) to the cohort with predominant left ventricular failure (LVF, n = 879), and 2) the MR patients who underwent valve surgery (n = 43) to those who did not (n = 51). RESULTS: Shock developed early after MI in both the MR (median 12.8 h) and LVF (median 6.2 h) cohorts. The MR patients were more often female (52% vs. 37%, p = 0.004) and less likely to have ST elevation at shock diagnosis (41% vs. 63%, p < 0.001). The MR index MI was more frequently inferior (55% vs. 44%, p = 0.039) or posterior (32% vs. 17%, p = 0.002) than that of LVF and much less frequently anterior (34% vs. 59%, p < 0.001). Despite having higher mean LVEF (0.37 vs. 0.30, p = 0.001) the MR cohort had similar in-hospital mortality (55% vs. 61%, p = 0.277). The majority of MR patients did not undergo mitral valve surgery. Those undergoing surgery exhibited higher mean LVEF than those not undergoing surgery; nevertheless, 39% died in hospital. CONCLUSIONS: The data highlight opportunities for early identification and intervention to potentially decrease the devastating mortality and morbidity of severe post-myocardial infarction MR.

The pulmonary venous systolic flow pulse--its origin and relationship to left atrial pressure.

OBJECTIVES: The purpose of this study was to determine the origin of the pulmonary venous systolic flow pulse using wave-intensity analysis to separate forward- and backward-going waves. BACKGROUND: The mechanism of the pulmonary venous systolic flow pulse is unclear and could be a "suction effect" due to a fall in atrial pressure (backward-going wave) or a "pushing effect" due to forward-propagation of right ventricular (RV) pressure (forward-going wave). METHODS: In eight patients during coronary surgery, pulmonary venous flow (flow probe), velocity (microsensor) and pressure (micromanometer) were recorded. We calculated wave intensity (dP x dU) as change in pulmonary venous pressure (dP) times change in velocity (dU) at 5 ms intervals. When dP x dU > 0 there is a net forward-going wave and when dP x dU < 0 there is a net backward-going wave. RESULTS: Systolic pulmonary venous flow was biphasic. When flow accelerated in early systole (S1), pulmonary venous pressure was falling, and, therefore, dP x dU was negative, -0.6 +/- 0.2 (x +/- SE) W/m2, indicating a net backward-going wave. When flow accelerated in late systole (S2), pressure was rising, and, therefore, dP x dU was positive, 0.3 +/- 0.1 W/m2, indicating a net forward-going wave. CONCLUSIONS: Pulmonary venous flow acceleration in S1 was attributed to a net backward-going wave secondary to a fall in atrial pressure. However, flow acceleration in S2 was attributed to a net forward-going wave, consistent with propagation of the RV systolic pressure pulse across the lungs. Pulmonary vein systolic flow pattern, therefore, appears to be determined by right- as well as left-sided cardiac events.

Inter- and intrasubject variation in diazepam free fraction.

The extent of intersubject variation in diazepam free fraction was measured in fasting plasma of 74 unrelated subjects. Free fraction differences between subjects were significant and ranged from 0.97% to 1.99%. Diazepam free fraction in 29 males was normally distributed about a mean of 1.25% (range, 1.05% to 1.47%), but the distribution in females was skewed to higher free fractions and 40% had values above the highest in males. Albumin concentration (r = -0.27, p less than 0.002) and age (r = 0.44, p less than 0.001) only accounted for a small part of the variation. Within-pair variances were not greater in 11 dizygotic than in 18 monozygotic twin pairs, indicating a greater contribution of environmental than of genetic factors to diazepam binding. The prehemodialysis free fractions of diazepam in 9 uremic patients ranged from 3.44% to 6.69%, and decreased (p less than 0.005) in 7 after 6 hr of hemodialysis. In 10 subjects determination of intrasubject variation in diazepam free fraction between 14-hr fasting and 2-hr postprandial plasma samples indicated that because subjects differ in their pattern of change in free fraction (p less than 0.001), the overall decrease in mean free fraction did not achieve statistical significance (p = 0.10). The mean relative percent change in free fraction within subjects after feeding was 15.2%.

Drug-plasma protein binding in Kutchin Athapaskan indians.

Free fractions of diazepam (D alpha), warfarin (W alpha), and methadone (M alpha) were measured in plasma obtained from 37 Kutchin Athapaskan Indians. Mean D alpha (3.42%) varied directly with free fatty acid concentration (r = 0.65, P less than 0.001) and was higher than previously found in other groups. These higher levels of fatty acids were associated with lower W alpha (r = -0.43, P = 0.007), and W alpha rose with time after a meal (r = 0.42, P = 0.01) when fatty acids usually fall. Mean W alpha was 0.72% and increased with age (r = 0.47, P = 0.004). In multivariate analysis, age, fatty acids, and time after the last meal together accounted for 42% of intersubject variation in W alpha. W alpha and D alpha were inversely correlated (r = -0.33, P = 0.04), a result of the strong effects of fatty acids in these drugs. In contrast to both D alpha and W alpha, intersubject differences in M alpha correlated inversely with alpha 1-acid glycoprotein concentration (r = -0.50, P = 0.001), but not fatty acids.

Methadone binding to orosomucoid (alpha 1-acid glycoprotein): determinant of free fraction in plasma.

The distribution of basic drugs in blood differs qualitatively from that of acidic drugs. The binding of racemic, d-methadone, and l-methadone to human plasma and isolated protein fractions was studied by equilibrium dialysis at 37 degrees. In plasma samples from 29 healthy subjects free fraction of dl-methadone was (mean% +/- SD) 10.62 +/- 1.43. There were significant variations among subjects (p less than 0.001). The free fraction of the d-isomer was 9.24 +/- 1.61% and of the l-isomer, 12.44 +/- 1.53%. Plasma albumin concentration and degree of binding do not correlate, but in normal hypoalbuminemic subjects the free fraction of dl-methadone correlates negatively with the concentration of alpha 1-acid glycoprotein (alpha 1-AGP), an acute-phase reactant protein. Percentage dl-methadone bound to purified human serum albumin (HSA) (4.1 mg/dl) was 36.60% (mean +/- SD). Isolated alpha 1-AGP bound dl-methadone more avidly. As the alpha 1-AGP increased from 0.05 to 2.0 gm/l, free fraction fell from 92.40% to 8.80%. Addition of alpha 1-AGP (0.05 to 2.0 gm/l) to a physiologic concentration of purified HSA or to whole plasma progressively increased methadone binding. In eight monozygotic twin pairs, within-pair differences in binding of dl-methadone were less than in eight dizygotic twin pairs. Less than 20% of naloxone, codeine, morphine, heroin, pentazocine, and diphenoxylate bound to alpha 1-AGP. Elevations of alpha 1-AGP that occur in a variety of diseases may alter the kinetic and pharmacologic activity of methadone.

Warm retrograde cardioplegia. Protection of the right ventricle in mitral valve operations.

Hypothermia is believed to be the most important aspect of successful myocardial protection with retrograde coronary sinus cardioplegia. Because nutritive capillary flow to the right ventricle and septum is thought to be diminished with retrograde perfusion, these areas of the myocardium are considered at higher risk for intraoperative deterioration without the added protection of hypothermia. Recently we introduced warm aerobic arrest as an alternative to conventional methods of myocardial protection. We present our clinical results in 37 patients with mitral valve disease (+/- aortic valve, aortic root, or coronary artery disease) who underwent various cardiac procedures for which warm blood cardioplegic solution was delivered continuously via the coronary sinus after antegrade arrest. Thirty-five of the patients were in New York Heart Association class III or IV, and 19 patients had grade 3 or grade 4 left ventricular function. Sixteen patients had pulmonary hypertension, three with suprasystemic pressures, and marked right ventricular hypertrophy. Two patients had associated left ventricular hypertrophy. Nearly all patients returned to normal sinus rhythm shortly after removal of the aortic crossclamp, and they were easily discontinued from cardiopulmonary bypass even with crossclamp times of 3 hours. The 30-day hospital mortality rate was 2.7%. The perioperative myocardial infarction rate was 5.4%, and the prevalence of low-output syndrome was 10.8%. The results suggest that retrograde coronary sinus perfusion of blood cardioplegic solution at 37 degrees C is an effective method of myocardial protection even in patients with pulmonary hypertension at high risk for right ventricular failure. Its efficacy in this circumstance does not reside in its ability to deliver hypothermia.

The use of milrinone in pre-transplant assessment of patients with congestive heart failure and pulmonary hypertension.

BACKGROUND: Pulmonary hypertension in patients with congestive heart failure (CHF) is a risk factor for increased mortality after orthotopic cardiac transplantation. Reversibility of elevated pulmonary vascular resistance (PVR) by pharmacologic agents predicts improved outcomes. Milrinone, a phosphodiesterase inhibitor with vasodilating and positive inotropic properties, has been shown to lower PVR in one previous study. However, no study has documented outcomes after cardiac transplantation in patients in whom reversibility of pulmonary hypertension was demonstrated after administration of milrinone. METHODS: We retrospectively reviewed 19 patients with CHF and pulmonary hypertension defined as PVR > or = 3 Wood units, PVRI (pulmonary vascular resistance index) > or = 4 resistance units, or TPG (transpulmonary gradient = mean pulmonary artery pressure--mean capillary wedge pressure) > or = 12 mmHg being assessed for cardiac transplantation. A sub-group of 14 patients with severe pulmonary hypertension defined as PVR > or = 4, PVRI > or = 6 and TPG > or = 15 was also examined. Milrinone was administered as a bolus (50 ug/kg) and hemodynamic parameters were measured at 5, 10 and 15 minutes. Six patients received cardiac transplants. RESULTS: Administration of milrinone significantly lowered PVR, PVRI, mean pulmonary artery pressure (PAM)(all p = 0.002) and pulmonary capillary wedge pressure (PCWP)(p = 0.006). Cardiac output (CO) increased significantly (p = 0.001). TPG did not change (p = 0.33). In patients with severe pulmonary hypertension, the magnitude of these changes was greater. In addition, TPG was significantly lowered (p = 0.02). CONCLUSION: Milrinone lowered PVR by decreasing PAM and increasing CO significantly. In addition, PCWP was significantly lowered. These finding confirm both vasodilatory and inotropic effects of milrinone. Patients with severe pulmonary hypertension had more pronounced effects. There were no deaths in the group of patients proceeding to cardiac transplantation. Our study demonstrates the efficacy of milrinone in lowering PVR as well as suggesting safety in use in patients undergoing cardiac transplantation.

Effect of immunosuppressive therapy, serum creatinine, and time after transplant on plasma total homocysteine in patients following heart transplantation.

OBJECTIVES: To determine the prevalence of hyperhomocysteinemia in heart transplant recipients, and to assess the effect of renal function and immunosuppressive medication on total plasma homocysteine (tHcy) levels. BACKGROUND: Elevated plasma tHcy levels have been associated with increased risk of mortality in patients with established coronary artery disease. Graft coronary disease is the major cause of morbidity and mortality in long-term survivors of heart transplantation. The tHcy has been found to be elevated in heart and kidney transplant patients, however, the etiologic factors have not been clearly delineated. METHODS: The study group consisted of 70 heart transplant recipients (56 males, 14 females, mean age 53+/-13 years [range 17 to 69 years]). The parameters evaluated were fasting tHcy level, cumulative cyclosporine (CyA) dose, cumulative prednisone dose, serum creatinine, and time from transplantation. RESULTS: The mean fasting tHcy level was 20.5+/-10.2 micromol/L (range 5.2 to 59.0 micromol/L). Sixty-one (87%) had fasting tHcy levels greater than the seventy-fifth percentile of the general population (>12.2 micromol/L in males, and >10.1 micromol/L in females). There was no difference in mean post-transplant tHcy level between patients with and without coronary artery disease before transplantation (21.0+/-11.4 vs. 19.3+/-6.7 micromol/L, p = NS). There were significant relationships between the tHcy level and the serum creatinine (r = 0.76, p<0.001), and cumulative exposure to CyA (r = 0.31, p<0.01). There were no significant relationships between tHcy levels and cumulative prednisone dose, or time from transplantation. CONCLUSIONS: Fasting tHcy levels are markedly elevated in the majority of patients following heart transplantation, and are correlated to serum creatinine. Further studies are needed to determine other etiologic factors of elevated tHcy following heart transplantation, and to examine the impact of elevated tHcy on clinical outcomes.

Effective treatment of hyperhomocysteinemia in heart transplant recipients with and without renal failure.

BACKGROUND: Elevated total plasma homocysteine (tHcy) levels have been associated with vascular disease and higher mortality in patients with coronary artery disease. Graft coronary disease is a major cause of mortality in long-term survivors of heart transplantation, and hyperhomocysteinemia may be one of its causes. The objectives of our study were to establish the effectiveness of a 3 stage homocysteine-lowering algorithm in a group of 84 heart transplant (HTx) patients and to evaluate the effect of renal function on the response to homocysteine-lowering therapy. METHODS: Prospective treatment of 84 Htx patients (64 male; mean age, 48 +/- 13 years) with tHcy > 75th percentile consisted of a 3-stage treatment algorithm: Stage 1, folic acid (FA) 2 mg + vitamin (vit) B(12) 500 mcg daily; Stage 2, addition of vit B(6) 100 mg daily; Stage 3, increase FA to 15 mg daily. Serum creatinine (Cr) and tHcy levels were measured before treatment and 21 +/- 19 weeks after each stage of treatment. RESULTS: All 3 stages of treatment significantly lowered mean tHcy from 22.4 +/- 16.3 (mean +/- SD) micromol/liter to 16.3 +/- 6.7 micromol/liter (p < 0.00001), from 17.6 +/- 6.1 micromol/liter to 15.2 +/- 5.3 micromol/liter (p < 0.0001), and from 16.8 +/- 5.2 micromol/liter to 15.6 +/- 5.3 micromol/liter (p < 0.05), respectively. The average reduction from baseline was 38%. Creatinine levels did not change significantly during the study period. Total plasma homocysteine levels decreased below the 75th percentile in 55% of patients, with Cr levels significantly lower in this group of patients (126 +/- 36 micromol/liter vs 182 +/- 65 micromol/liter, p < 0.00001). However, we found no significant relationship between % change in tHcy and baseline Cr. CONCLUSIONS: In a group of 84 heart transplant patients with tHcy levels >75th percentile, treatment with FA and vit B(6) and B(12) according to a 3-stage algorithm resulted in statistically significant declines in mean tHcy levels. Overall, tHcy levels decreased 38%, with target tHcy levels <75th percentile achieved in 55% of the patients. The % change in tHcy was not related to Cr. Further studies are needed to correlate treatment of hyperhomocysteinemia with clinical endpoints, such as the time to development of transplant vasculopathy and long-term survival, and to define the most appropriate targets for therapy.

Normothermic ischemia in coronary revascularization.

Warm heart surgery-continuous perfusion with normothermic blood cardioplegia-was introduced as an alternative to conventional intermittent hypothermic perfusion for myocardial protection. Interruption of global coronary flow, however, greatly facilitates the performance of distal coronary anastomoses and is the method that has evolved with many surgeons using warm blood cardioplegia for coronary revascularization. We present results (mean +/- SD) in 720 patients undergoing coronary bypass surgery protected with intermittent warm blood cardioplegia and exposed to normothermic ischemia but with electromechanical arrest. An average of 3.2 +/- 0.9 grafts were constructed per case with an average aortic cross clamp time of 61.8 +/- 22.2 minutes. Cardioplegia was interrupted a total of 28.5 +/- 12.4 min per operation. The percent time off cardioplegia (PTOC) expressed as a proportion of the cross clamp was 48.2 + 18.6%. The longest single time off cardioplegia (LTOC) was 11.4 +/- 4.0 min per patient. Calculated mean cardioplegia delivery during the cross clamp period was 75 ml/min. PTOC and LTOC were divided into quartiles (PTOC: < 36, 36-49, 50-62, > 62%; LTOC: < 10, 10-11, 12-13, > 13 min) and related to prespecified composite outcome of mortality, enzymatic myocardial infarct and low output syndrome. PTOC was protective (event rate/quartile 16.1%, 17.2%, 9.4%, 10.6%, p = 0.07) and longer LTOC (event rate/quartile 13.5%, 10.3%, 10.9%, 19.0%, p = 0.046) borderline harmful. The data suggest that when necessary multiple periods of normothermic myocardial ischemia in the presence of electromechanical arrest are well tolerated and potentially protective provided that any single ischemic interval is < 13 min.

Contribution of cardiogenic oscillations to gas exchange in constant-flow ventilation.

The contribution of cardiogenic oscillations to gas exchange during constant-flow ventilation was examined in 11 dogs. With the use of two variations of cardiopulmonary bypass to maintain the systemic and pulmonary circulation, the influence of cardiogenic oscillations was removed by arresting the heart. Cardiac arrest by ventricular fibrillation was associated with a mean decrease in alveolar ventilation of 43% in five dogs on right and left heart bypass. However, successful defibrillation and return of the prearrest level of alveolar ventilation could not be achieved; thus we studied six dogs on left heart bypass. Alveolar ventilation decreased an average of 37% with cardiac arrest, and defibrillation resulted in a return of alveolar ventilation to 81% of the prearrest value. These results are consistent with previous predictions that cardiogenic oscillations are an important mechanism of gas transport during constant-flow ventilation.

Warm heart surgery and results of operation for recent myocardial infarction.

Revascularization procedures after recent myocardial infarction are associated with higher mortality and morbidity compared with elective coronary artery bypass grafting. Traditional methods of myocardial protection impose a further ischemic insult on already compromised myocardium. Continuous cold blood cardioplegia may eliminate ischemia but may still leave the heart anaerobic. Theoretically, warm aerobic arrest addresses both of these issues and may become an attractive alternative to standard hypothermic ischemic arrest in this setting. In 115 nonrandomized patients undergoing coronary artery bypass grafting within 6 hours to 7 days of an acute myocardial infarction, myocardial protection was provided with continuous cold (4 degrees C) or continuous warm (37 degrees C) blood cardioplegia. Fifty-one patients (after 1988) protected with warm blood cardioplegia were compared with a historical cohort of 64 patients (before 1988) protected with cold blood cardioplegia. Results indicate that the warm cardioplegia group had no mortality versus 10.9% for the cold group (p less than 0.05), a myocardial infarction rate of 2.0% in the warm versus 9.3% in the cold group, and use of intraaortic balloon pump of 0% versus 12.5%, respectively (p less than 0.05). It is concluded that continuous warm aerobic arrest may minimize ischemia and anaerobic metabolism during the operative procedure, and may be of benefit to patients who have a limited tolerance to ischemic insult.

Pericardial repair of a tracheal laceration during transhiatal esophagectomy.

Transhiatal esophagectomy has recently been popularized for both benign and malignant esophageal disease. While we were performing a transhiatal esophagectomy for a squamous cell cancer of the upper third of the esophagus, a tear in the membranous trachea near the carina occurred. This was repaired through the cervical incision with a free pericardial patch. This solution to a potentially catastrophic complication of transhiatal esophagectomy gave a satisfactory result without early or late postoperative respiratory complications.

Warm heart surgery: experience with long cross-clamp times.

Although hypothermic cardioplegic arrest prolongs the period of ischemic arrest by reducing oxygen demands, it leaves the heart dependent solely on anaerobic metabolism for its energy demands and exposes it to the detrimental effects of hypothermia. Consequently, myocardial protection is compromised, and safe aortic occlusion time is limited to 120 minutes. As electromechanical arrest accounts for 90% of myocardial oxygen consumption, we hypothesized that an ideal state of the heart might be chemically arrested and perfused with warm blood, ie, aerobic arrest. We applied this approach to myocardial protection in 308 consecutive procedures. To assess the adequacy of this method, we reviewed the results in a group of 22 patients in whom the aortic cross-clamp time was, of necessity, greater than or equal to 3 hours (mean time, 204 minutes; range, 180 to 393 minutes). Nineteen of the patients represented a high operative risk with grade 3 or 4 left ventricular function and New York Heart Association class III or IV. All hearts resumed spontaneous normal sinus rhythm without defibrillation, and 21 patients were easily weaned from bypass within minutes of removal of the aortic cross-clamp without inotropic or intraaortic balloon pump support. Mortality was 4.5%, low-output syndrome occurred in 4.5%, and there were no perioperative myocardial infarctions. Our results suggest that warm aerobic arrest is safe and effective in prolonged high-risk procedures, virtually eliminating the period of ischemia, limiting the period and injury of reperfusion, and abolishing the detrimental effects of hypothermia.

Effect of lung inflation and sternotomy direction on pleural space violation.

Patients often are disconnected temporarily from the ventilator before sternotomy to avoid entering the pleural space with the sternal saw. Although this practice is widespread, it is based on questionable physiologic principles. To evaluate the efficacy of this maneuver in reducing the incidence of pleural space violation with first-time sternotomy, 126 cardiac patients were randomized prospectively to either lungs inflated or deflated during sternotomy with the surgeon blinded to the particular assignment. The incidence of pleural space violation overall was 12%, occurring in 15% of patients with deflated lungs and in 9% of those with inflated lungs (p = 0.455 by chi 2 test). Examining the effect of the direction of sternotomy on pleural space entry revealed a 4% incidence with sternotomy starting at the xiphoid versus a 21% incidence with sternotomy starting at the sternal notch (p = 0.009 by chi 2 test). Preexisting hyperinflation of the lungs as evaluated by chest radiograms did not influence the incidence of pleural space violation. To reduce pleural space violation, sternotomy should be performed from the xiphoid to the sternal notch. More importantly, disconnecting the patient from the ventilator does not reduce pleural space violation with sternotomy and its further use is not indicated. These findings are discussed in the context of relevant heart-lung pathophysiology.

Retrograde continuous warm blood cardioplegia: a new concept in myocardial protection.

This report presents the results in our first clinical series of patients receiving continuous warm blood cardioplegia through the coronary sinus. Warm oxygenated blood cardioplegia has certain theoretical advantages, such as continuously supplying oxygen and substrates to the arrested heart while avoiding the side effects of hypothermia. Retrograde infusion of cardioplegia also offers certain advantages (eg, in valve operations and in patients with severe coronary artery disease) that are complementary to warm blood cardioplegia. Retrograde warm blood cardioplegia was used in 113 consecutive patients (85 men and 28 women with a mean age of 61 years) undergoing various procedures. Three percent of the patients died, 7% needed transient intraaortic balloon pump support, 6% had evidence of perioperative myocardial infarction, and 96% had spontaneous return of rhythm. There were no coronary sinus injuries. This new technique of retrograde continuous warm blood cardioplegia is a simple, safe, and reliable method of myocardial protection that may change the way we currently protect the heart intraoperatively.

Myocardial protection in the hypertrophied right ventricle.

Hypertrophied right ventricle presents a sensitive state that may not be adequately protected by modern cardioplegic methods. Cardiac metabolism, performance, and ultrastructure were measured in response to 1 hour of cardioplegic arrest in 15 pigs with right ventricular hypertrophy using intermittent hypothermic crystalloid, blood, and Flusol DA 20%-based cardioplegia. Reperfusion time was 1 hour. One hour after a 60-minute cross-clamp period, there were no differences in light microscopy. Total energy stores increased in 4 of 5 animals given blood cardioplegia compared with 1 of 5 for each of the other groups. Cardiac performance data also showed better results for animals treated with blood cardioplegia. After 30 minutes of reperfusion, animals receiving blood cardioplegia recovered 131% +/- 42% of preoperative systolic performance compared with 106% +/- 49% for Fluosol-treated animals and only 82% +/- 27% recovery for the crystalloid-treated group. After 60 minutes of reperfusion, the blood group showed 119% +/- 20% recovery compared with 89% +/- 23% and 85 +/- 50% recovery for Fluosol- and crystalloid-treated hearts, respectively. In conclusion, blood cardioplegia provided better protection than did crystalloid or Fluosol DA 20% cardioplegia when animals with right ventricular hypertrophy underwent 1 hour of cardioplegic arrest. It may have repaired damaged myocardium, leaving better hearts after cross-clamping than before.

Cardiovascular effects of positive pressure ventilation in humans.

Pulsus paradoxus is the pathological exaggeration of the normal transient decrease in arterial blood pressure that occurs during spontaneous inspiration. The transient increase in arterial pressure associated with positive pressure inspiration is termed reversed pulsus paradoxus (RPP). Cardiorespiratory interactions and the mechanism of these effects have been studied extensively in animals, and to a lesser extent, in humans. In this clinical investigation pulsus paradoxus and RPP were studied in 10 postoperative cardiac patients with invasive monitoring and mediastinal pressure catheters placed intraoperatively. From end-expiration to end-inspiration, RPP was accompanied by decreased transmural pressures in the right atrium, left atrium, and aorta. Left ventricular end-systolic volume measured by radionuclide studies diminished during a positive pressure inspiration, without a significant change in end-diastolic volume. These results are consistent with decreased left ventricular afterload as the major mechanism of RPP. During spontaneous breathing, inspiration was associated with converse effects, a fall in arterial pressure and an increase in transmural right atrial, left atrial, and aortic pressures from end-expiration to end-inspiration. End-systolic volume was significantly larger at end-expiration than end-inspiration, with no change in end-diastolic volume. These findings suggest that an increase in left ventricular afterload during inspiration is responsible for the observed pulsus paradoxus.

Clinical performance of biological and mechanical prostheses.

Prosthetic valve replacement remains the most viable alternative for the treatment of severely diseased heart valves. The cumulative experience of mechanical protheses and bioprostheses was evaluated for a 10-year performance comparison: Carpentier-Edwards standard porcine bioprosthesis (CE-S), 1,214 operations; Carpentier-Edwards supraannular porcine bioprosthesis (CE-SAV), 2,489; and mechanical prostheses, 1,364 operations (St. Jude Medical, Carbomedics, Duromedics, and Björk-Shiley Monostrut). The freedom from thromboembolism and hemorrhage at 10 years was 82% for CE-S, 78% for CE-SAV, and 65% for mechanical prostheses (p < 0.05). The relationship existed for major thromboembolism and hemorrhage, 91% (CE-S), 87% (CE-SAV), and 88% (mechanical) (p < 0.05), without clinical relevance. The freedom from structural valve deterioration and valve-related reoperation favored mechanical prostheses (p < 0.05) at 10 years (structural failure: 78% for CE-S, 81% for CE-SAV, and 99% for the mechanical group; reoperation: 74% for CE-S, 76% for CE-SAV, and 88% for mechanical prostheses). The freedom from fatal reoperation was not clinically different: 96% for CE-S, 99% for CE-SAV, and 99% for mechanical prostheses (p < 0.05) at 10 years. The freedom from valve-related mortality was not different (p = not significant) at 10 years: 87% for CE-S; 92% for CE-SAV; and 91% for mechanical. The freedom from permanent impairment or residual morbidity, primarily from thromboembolism, was 95% for CE-S, 92% for CE-SAV, and 95% for mechanical group (p < 0.05) but not clinically relevant.(ABSTRACT TRUNCATED AT 250 WORDS)