Biomedical subjects
Publications and source records attributed to G Bloch.
We describe a simple technique for optimizing oxygen delivery during normothermic continuous blood cardioplegia. It involves the use of a minimal volume of cardioplegic agents, the infusion rate of which is adjusted so as to keep the heart arrested. The resulting enhancement of oxygen supply is marshalled from the maintenance of hematocrit values in the range of 0.25.
Peripheral vasodilation is commonly seen during and after warm heart operations and can become of clinical concern when it requires vasopressors because some of these drugs adversely affect coronary artery bypass graft flows. As hemodilution lowers systemic vascular resistance, we assessed whether peripheral vasodilation could be limited by a drastic reduction of the volume of infused cardioplegia. Fifty patients underwent isolated coronary artery bypass grafting procedures using normothermic (35 degrees to 37 degrees C) bypass and normothermic continuous retrograde blood cardioplegia. They were divided into two equal groups: in group 1, blood was diluted 4:1 with hyperkalemic crystalloid cardioplegia, whereas in group 2, the cardioplegic "solution" was limited to the sole arresting agents that were concentrated in a small volume (16 mEq potassium chloride and 3 mEq magnesium chloride in a 20-mL ampoule). This "mini-cardioplegia" was continuously added to arterial blood so as to keep the heart arrested. The average volume of cardioplegia per patient was 1,000 mL in group 1 and 58 mL in group 2 (p < 0.0001). The mini-cardioplegia technique resulted in a reduced incidence of perioperative systemic vasodilation: group 2 patients required significantly less vasopressors (p < 0.05) and less volume loading, as reflected by significantly lower right atrial and pulmonary capillary wedge pressures (p < 0.05 and p < 0.03 at 12 hours postoperatively, respectively), compared with group 1 patients who received traditional high-volume cardioplegia. There were no differences between the two groups with respect to myocardial recovery, as assessed by standard clinical and hemodynamic end points.(ABSTRACT TRUNCATED AT 250 WORDS)
A controversy persists as to whether cardiopulmonary bypass (CPB) decreases plasma levels of triiodothyronine (T3), thereby justifying peri-operative administration of T3 to improve haemodynamic recovery. To examine the effects of T3 therapy on post-CPB haemodynamics and to determine whether the potential inotropic effects of T3 are mediated by an increase in beta-adrenergic responsiveness, a prospective, randomized, double-blind, placebo-controlled study was performed in 20 patients undergoing cardiac surgery with CPB. T3 or placebo solution (10 patients in each group) was given intravenously at the time of aortic unclamping and 4, 8, 12 and 20 h thereafter. End points included (1) thyroid hormone levels measured by radioimmunoassay (2) standard haemodynamic parameters (3) the density of lymphocyte beta-adrenoceptors measured by a radioligand (125I-iodocyanopindolol) binding technique. Post-CPB values (cross clamp removal) of T3 (pg.ml-1) were not significantly decreased compared with pre-CPB values: 3.3 +/- 0.2 vs 3.1 +/- 0.2 in controls and 3.3 +/- 0.4 vs 3.7 +/- 0.6 in T3-treated patients, respectively. The haemodynamic parameters were no different between the two groups at any postoperative time point. Likewise, density and affinity of lymphocyte beta-adrenoceptors were not significantly different from pre-operative values in either group. Thus, there seems to be no sound justification for a routine use of T3 in patients undergoing open-heart procedures.
In the course of cardiac transplantation, donor hearts undergo a four-step sequence of events (arrest, cold storage, global ischemia during implantation, and reperfusion) during which myocardial damage can occur. We tested the hypothesis that the functional recovery of these hearts could be improved by exposure to two interdependently formulated preservation solutions throughout this four-step sequence. Solution I was used as a perfusion and storage medium during the first three steps, and solution II served as a modified reperfusate. The two solutions share the following principles of formulation: prevention of cell swelling (high concentrations of mannitol, a myocardium-specific impermeant) calcium overload (ionic manipulations), and oxidative damage (reduced glutathione) and enhancement of anaerobic energy production (glutamate). The two solutions differ with respect to the calcium content and buffering capacity. One hundred rat hearts perfused with isolated isovolumic buffer were subjected to cardioplegic arrest; cold (2 degrees C) storage for 5 hours, global ischemia at 15 degrees C for 1 hour, and normothermic reperfusion for 1 additional hour. In a first series of experiments (70 hearts), our kit of solutions was compared with six clinical preservation regimens that involved cardiac arrest with St. Thomas' Hospital or University of Wisconsin solutions followed by storage of the hearts in saline, Euro-Collins, St. Thomas' Hospital, or University of Wisconsin solutions. In a second series of experiments (30 hearts), the effects of the kit were more specifically investigated in relation to two types of additive--oncotic agents (dextran) and thiol-based antioxidants (reduced glutathione and N-acetyl-L-cysteine). According to comparisons of maximal rate of ventricular pressure increase and left ventricular compliance after reperfusion, the best myocardial protection was afforded by our kit of solutions. The addition of dextran during storage did not provide additional protection. Conversely, the omission of reduced glutathione was clearly detrimental; the replacement of reduced glutathione with N-acetyl-L-cysteine failed to improve recovery beyond that provided by antioxidant-free solutions, thereby suggesting the importance, in this model, of an anti-free radical compound that, like reduced glutathione, is operative extracellularly. We conclude that the preservation of heart transplants can be improved with the sequential use of two closely interrelated solutions, the formulations of which integrate the basic principles of organ preservation with those of myocardium-specific metabolism.
In an attempt to provide a consistent protection of cardiac allografts during the sequence of events inherent in transplantation procedures, we developed two preservation solutions of which one is used for initial arrest, storage and cardioplegia during graft implantation, whereas the other serves as initial reperfusate. The formulations of these solutions are closely interrelated and their design has integrated the basic principles of organ preservation with those of myocardium-specific metabolism. Based upon experimental studies in the isolated rat heart model, this integrated approach has yielded better functional recoveries than conventional preservation protocols.
The enthusiastic clinical reports on normothermic blood cardioplegia contrast with the paucity of data on the myocardial metabolic effects of this technique. The present study was therefore designed to assess whether normothermic blood cardioplegia really provides an aerobic environment during aortic cross-clamping. Thirty-one patients undergoing coronary (16 patients), valve (13 patients), and transplantation (2 patients) procedures were given continuous normothermic blood cardioplegia through the coronary sinus. Myocardial metabolism was assessed either immediately before aortic unclamping (16 patients) by collecting blood simultaneously from the cardioplegia infusion line and the aortic effluent or during reperfusion (15 patients) by collecting blood simultaneously from the radial artery and the coronary sinus. All samples were assayed for markers of anaerobiosis (blood gases, lactates), leukocyte activation (elastase), and lipid peroxidation (malondialdehyde, vitamin E). At the end of arrest, oxygen extraction was low, whereas the production of lactates was small, thereby suggesting the efficacy of normothermic blood cardioplegia in maintaining a predominantly aerobic metabolism. This was confirmed by postarrest data, as oxygen extraction measured immediately after cross-clamp removal was unchanged from prearrest values, whereas lactate metabolism yielded transient and limited production followed by prompt recovery of normal extraction patterns. There was no release of elastase from the myocardium, which suggests adequate protection of the coronary endothelium from ischemic injury and the related increase in leukocyte activation. Likewise, postarrest coronary sinus concentrations of malondialdehyde and vitamin E were identical to the respective arterial concentrations, thereby ruling out the occurrence of intramyocardial lipid peroxidation at the time of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Age over 70 years and critical stenosis of the left main coronary artery trunk are two situations in which the use of the internal mammary artery has been questioned. Because the coexistence of these two conditions is increasingly seen, we reviewed our experience with 53 patients 70 years of age or older that underwent myocardial revascularization for left main disease. In 17 patients, the left anterior descending coronary artery was grafted with the left internal mammary artery whereas the 36 remaining patients were exclusively revascularized by means of saphenous vein conduits. There was no significant difference in postoperative mortality or morbidity between the two patient groups. We conclude that elderly patients with left main disease should be offered the benefits of a mammary artery graft provided they are hemodynamically stable.
Among the interventions designed to limit postischemic oxidative injury, those that enhance the myocardial content of thiol groups are attractive because thiols are powerful antioxidant. Indeed, part of the protection afforded by the angiotensin-converting enzyme (ACE) inhibitor captopril in regional myocardial ischemia is attributed to its thiol group. This study assesses the effects of captopril in a surgically relevant model of global ischemic arrest. Thirty rats were implanted subcutaneously (s.c.) with osmotic pumps that allowed continuous delivery of captopril (total dose 75 mg), enalapril (a nonthiol-containing ACE inhibitor, total dose 7.5 mg) or saline in 48 h. Drug concentrations were equipotent in their effect on angiotensin I (ANGI) pressor response. Hearts were then excised, perfused under isovolumic conditions, and subjected to 90-min cardioplegic arrest at 30 degrees C followed by 1-h reperfusion. Pre- and postischemic coronary flows were significantly higher to a similar extent in the two drug-pretreated groups than in controls. However, captopril-pretreated hearts had the best recovery of contractility (dP/dtmax; 3,590 +/- 74 versus 2915 +/- 64 mm Hg s-1 in the enalapril group, p less than 0.001), and diastolic pressure (13.7 +/- 0.9 mm Hg vs. 20.0 +/- 1.6 mm Hg in the enalapril group, p less than 0.05). We conclude that pretreatment with ACE inhibitors improves myocardial recovery after cardioplegic arrest and that captopril is more effective than enalapril. The additional protection afforded by captopril was not flow mediated, suggesting that the cardioprotective effects of this drug not only involve an ACE inhibition-dependent coronary vasodilation but could be related to a thiol-dependent limitation of oxidative injury.
Natural abundance 13C NMR (nuclear magnetic resonance) spectroscopy was used to distinguish patients suffering from muscle glycogenosis type V (McArdle's disease) from normal subjects by measuring their muscle glycogen content at rest. Proton-decoupled 13C spectra were obtained in 10-15 min from calf muscles at rest. The ratio of the glycogen/creatine signal areas was 12.9 +/- 1.7 in four McArdle's disease patients and 2.0 +/- 0.7 in seven normal subjects. This technique thus allows the non-invasive diagnosis of muscle glycogenosis.
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From 1981 to 1989, 65 patients over 80 years were submitted to surgery for severe calcific aortic stenosis. Thirteen patients were in NYHA II, 31 in NYHA III, 21 in NYHA IV. Mean valve area was 0.52 +/- 0.14 cm2 and mean aortic valve gradient was 62 +/- 18 mmHg. Left ventricular function was altered (ejection fraction less than 40%) in 33 patients. Six patients had a previous balloon aortic valvuloplasty. Bioprosthesis were used in all 65 patients associated to CABG (in 5) and mitral valve replacement (in 1). One month mortality was 19 cases (29%) due to cardiac failure (in 10) pulmonary (in 7) and neurological (in only 2) complications. Early mortality was nearly significantly correlated to NYHA stage (p = 0.08) and preop renal insufficiency (p = 0.07). It was significantly correlated to function (40% mortality when ejection fraction less than 40%, 16% in others) and to operations on emergency basis (5 deaths over 6). Hospital morbidity was 68%. There were 5 late deaths. Among the 41 long-term survivors (3 mths-7yrs) 29 are in NYHA I, 10 in NYHA II and 2 in NYHA III due to valve failure. The actuarial survival probability is 65% at one year, 50% at 5 years. In summary good long-term results justify to take a high post operative risk in octogenarians. Early surgery before left ventricular impairment improves the survival.
From 1981 to 1989, 60 patients more than 80 years of age were referred for operation for severe calcific aortic stenosis. All patients were symptomatic: 13 in New York Heart Association (NYHA) functional class II, 28 in class III, and 19 in class IV. The preoperative mean cardiothoracic ratio was 0.58 +/- 0.09; the mean valve area, 0.52 +/- 0.14 cm2; and the mean aortic valve gradient, 62 +/- 18 mm Hg. Left ventricular function was impaired in 30 patients (ejection fraction less than 0.40). Coronary arteriography was performed in 10 patients. Aortic replacement used bioprosthesis in all 60 patients associated with aortocoronary bypass (in 5) and mitral valve replacement (in 1). One-month mortality rate was 28% (17 patients) due to cardiac failure (in 9), pulmonary complications (in 6), and neurological complications (in 2). Early mortality was not correlated with preoperative angina, cardiothoracic ratio, associated operation, and cross-clamping time. It was not obviously correlated with preoperative functional class but correlated positively with urgent operations and with left ventricular function (40% mortality in patients with ejection fraction less than 0.40 versus 16% mortality in others). Hospital morbidity was 68%. Mean hospitalization was 15 +/- 7 days. There were four late deaths. Thirty-nine patients are long-term survivors (3 months to 7 years): 27 in class I, 10 in class II, and 2 in class III due to primary valve failure. The actuarial survival probability is 65% at 1 year and 61% at 5 years. In summary, the good long-term quality of life justifies the high postoperative risk in octogenarians. Early operation before cardiac function impairment improves the results.
The regain of interest in aortic homograft bioprostheses is related to the prospects of improved viability resulting from explanation from organ donors, preservation in rich tissue culture media, together with the progress made in techniques of cryopreservation. Viability studies examining morphology of electron microscopy and tests of tissue culture confirm this notion of longer viability. These properties raise hopes of satisfactory long-term results while acknowledging outstanding antigenic problems which require strict A-B-O system compatibility. The results of a preliminary series of 42 valve homografts implanted at Henri Mondor Hospital over the last 5 years are reported. Twenty-one bioprostheses were implanted on the right side in congenital heart disease with good results in every case. Twenty-one were implanted in the aortic position in children and show no signs of degeneration as yet. One poor result was related to a technical error in calibration. The rebirth of this technique raises certain hopes, especially in aortic valve replacement.
The renewed interest in valvular homograft is due to the new concept of their viability. This viability requires procurement from organ donors and preparation in rich tissue culture medium immediately prior to cryopreservation. This viability, confirmed by morphological tests especially electron microscopy, and by cell culture tests is the basis for satisfactory long-term results. Antigenic aspects justify rigorous respect of A-B-O compatibility. A preliminary clinical series of 35 valvular homografts (16 on the right side and 19 in the aortic position), implanted especially in children over the last five years at the Henri Mondor Hospital, is reported here, No tissue failures have been reported to date.
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Long-term performance of the first one hundred bioprostheses (BP) implanted was evaluated in 100 patients (pts) surviving isolated aortic valve replacement, mitral valve replacement and tricuspid replacement from October 1975 to March 1978. Follow-up was always more than 10 years. Cumulative duration of follow-up was 7,048 months. Follow-up ranged from 112 to 139 months. Overall late mortality was 16.13 thromboembolic episodes occurred in 11 pts. Reoperation was performed in 14 pts due to primary tissue failure in 11 pts. 64 patients were free from mortality and valve-related reoperation.
From May, 1975, to December, 1988, 30 patients (pts), 26 men and 4 women, aged 36 to 79 (average age: 58) underwent one or several aortocoronary bypass (ACB) operations requiring the use of veins from the upper limbs (VUL). Sixty operations (2.0 ACB/pt) were performed, involving the anterior interventricular artery in 27 cases, the right coronary artery in 14 and the other left vessels in 19. The grafts used were a VUL in 45 cases, an internal mammary artery in 13, a great saphenous vein in one case and a 4-mm polyurethan tube in one case. The indications for the use of a VUL included bilateral stripping in 23 patients, repeated phlebitis in one, bilateral varices in 2, and the previous use of the saphenous veins in 4 patients. The coronary lesions were a three-vessel involvement in 17 cases, a two-vessel involvement in 9 and a single-vessel involvement in 4. An additional procedure was required in two patients for the resection of a left ventricular aneurysm and for the plication of an akinetic area of the left ventricle. No intraoperative complication was observed. Perioperative mortality was of two cases (6.6%). The postoperative myocardial infarction rate was of one case (3.3%). A complication directly associated with the type of graft used (massive bleeding due to graft tearing) caused cardiac arrest in one case. Two patients presented with local disorders caused by the removal of veins from the upper limbs, including hypoesthesia of the forearm in one case and anesthesia associated with regressive muscle enfeeblement in the other.(ABSTRACT TRUNCATED AT 250 WORDS)
We present proton and phosphorus NMR data, which contribute to explain why the 5-methylcytidine (m5C) differently affects the conformational transitions of CGUAm5CG (Bloch et al., FEBS Letters 219, 464 (1987)) and CGm5CGCG (Ceolin et al., J. Am. Chem. Soc. 109, 2539 (1987)). The atypical intermediate form observed in the random coil to A-like duplex transition of CGm5CGCG is determined: this original duplex structure exhibits a frame-shift pairing of the two strands, with a partial conservation of the A-type structure. In the case of CGUAm5CG such a pairing process would lead to a complete mismatch pairing. This feature probably explains that the NMR data of CGUACG and CGUAm5CG are similar and consistent with a random coil to A-type helix transition. Nevertheless a significant difference between the correlation times observed for the molecular motions of the two duplexes is detected. Another example of unusual conformational transition of methylated RNA oligomers is given by CAm5CGUG.