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PubMed1995

Efficiency of in vivo gene transfection into transplanted rat heart by coronary infusion of HVJ liposome.

BACKGROUND: Current methods of in vivo gene transfer into myocardium are limited by low efficiency. To improve in vivo gene transfer, a gene transfer method using hemagglutinating virus of Japan (HVJ) as a viral vector can be an alternative. METHODS AND RESULTS: In vivo gene transfection of FITC-labeled oligonucleotide (F-ODN) and cDNA of beta-galactosidase (beta-gal) was examined with use of the HVJ liposome (H group) or without it (C group). In the H group, F-ODN or cDNA of beta-gal were complexed with liposomes, DNA binding nuclear protein (HMG1), and the viral protein coat of HVJ. After the harvest of donor rat hearts arrested by cardioplegia, the coronary artery was infused with the liposome gene complex. The hearts were transplanted into the abdomens of recipient rats and harvested 3 days after transplantation. Regarding F-ODN, the H group clearly showed FITC staining in the nuclei of the myocytes and endothelial cells in almost all layers of the myocardium as compared with the C group. Regarding the expression of beta-gal, the H group showed a clear expression of beta-gal on myocytes, whereas very low expression of beta-gal was seen in the C group. CONCLUSIONS: The donor hearts were transfected with F-ODN and beta-gal gene in almost all layers of the myocardium as a result of coronary infusion of the HVJ liposome during cardioplegic arrest. Our method is seen as a novel in vivo gene transfer technique for the heart and may provide a new tool for both research and therapy of heart transplantation.

Animals↗
PubMed2006

On-pump beating-heart mitral valve plasty without aortic cross-clamping.

Patients with ischemic cardiomyopathy often have mitral regurgitation, which should be corrected for better long-term survival. Mitral valve surgery is usually performed during cardiopulmonary bypass under the arrested heart condition. The ascending aorta is cross-clamped and the heart is arrested using a cardioplegic solution. However, because ischemic cardiomyopathy patients often have a severely atherosclerotic ascending aorta and low cardiac function, aortic cross-clamping and cardiac arrest increase the risk of postoperative thromboemboli and low cardiac output syndrome. Under the on-pump beating-heart condition, we performed mitral valve plasty concomitant with coronary artery bypass grafting, tricuspid annuloplasty, left ventricular aneurysmectomy, and the maze procedure without aortic cross-clamping for a patient with ischemic dilated cardiomyopathy and bradycardial atrial fibrillation. The patient had no postoperative complications and re covered rapidly. Thus, to prevent serious postoperative complications, on-pump beating-heart mitral valve surgery without aortic cross-clamping may be a suitable surgical option for patients with ischemic cardiomyopathy.

Aged↗
PubMed1997

In situ visualization of spontaneous calcium waves within perfused whole rat heart by confocal imaging.

We describe the first direct visualization of Ca2+ oscillations in the perfused whole rat heart. Dye loading at a low temperature and enhanced optical-section techniques of confocal microscopy by elimination of the refractive index mismatch with use of saline-immersible objective lens enabled us to image multiple Ca2+ waves in the subepicardial myocardium of the fluo 3-loaded heart. These Ca2+ waves were sporadically seen even with a physiological extracellular Ca2+ perfusion in either a paced or an arrested heart and propagated beyond cellular boundaries within the three-dimensional structures of cardiac muscle. Under these conditions, the velocity of wave propagation was 60-100 microns/s and the frequency of initiation was relatively low (< 2 Hz). With an increase in extracellular Ca2+ concentration, however, the waves became more prevalent and tended to be multifocal, and an increasing fraction of the waves exhibited faster propagation velocities and higher frequencies. These results suggest that perfused rat hearts exhibit spontaneous Ca2+ waves in an apparently resting state and that under Ca(2+)-overload conditions the multifocal and high-frequency waves become more widespread in the heart syncytium, which may provide an understanding of the ionic basis for the summation of afterdepolarizations and triggering of arrhythmias seen under pathological conditions.

Aniline Compounds↗
PubMed1992

Effect of antibody to leukocyte adhesion molecule CD18 on recovery of neonatal lamb hearts after 2 hours of cold ischemia.

BACKGROUND: Prior studies have shown that leukocytes are important in reperfusion injury after normothermic ischemia, and recently discovered leukocyte adhesion molecules that bind to endothelial ligands may be involved in this process. No studies on the role of leukocyte adhesion molecules in hypothermic ischemia are available. METHODS AND RESULTS: We assessed the effect of preischemic administration of monoclonal antibody to the leukocyte adhesion molecule CD18 on recovery of isolated blood-perfused neonatal lamb hearts arrested for 2 hours with 15 degrees C K+ cardioplegic solution by comparing nine antibody-treated and nine control hearts. At 30 minutes after reperfusion, antibody-treated hearts compared with control hearts had better percent recovery of maximum left ventricular (LV) developed pressure (83.9 +/- 2.2% versus 73.6 +/- 3.0%, mean +/- SEM), LV dP/dt (78.4 +/- 3.3% versus 67.4 +/- 3.4%), coronary blood flow (159.5 +/- 12.2% versus 84.4 +/- 3.5%), and myocardial oxygen consumption (129.8 +/- 16.5% versus 71.2 +/- 6.2%) (all p < 0.05). In each heart, we also tested coronary vascular resistance (CVR) response to 10(-6) mol/l acetylcholine (ACh) infusion to assess endothelial function. Percent recovery of CVR response to ACh was higher in antibody-treated hearts (38.4 +/- 4.3%) than control hearts (13.4 +/- 12.8%) (p = 0.08). CONCLUSIONS: These results suggest that leukocyte adherence to endothelium mediated by CD18 plays an important role in reperfusion after hypothermic ischemia. Antibody to CD18 may be useful in myocardial and endothelial protection during surgically induced ischemia.

Animals↗
PubMed1985

Impairment of myocardial function induced by particulate contamination of cardioplegic solutions.

The U.S. Pharmacopoeia defines acceptable limits of particle contamination for intravenous solutions. Used conventionally, these solutions are filtered by the lungs, and there are few reports of particle-induced tissue injury to the systemic circulation. We have used an isolated rat heart model to assess whether unfiltered direct intraarterial administration of cardioplegic solutions, as in open-heart surgery, can be damaging to the myocardium. An intravenous solution of U.S. commercial manufacture was selected for evaluation. Particle-counting revealed this solution to be well within the U.S.P. limits. Direct intracoronary infusion of this solution at 20 degrees C and at constant pressure led to an approximate 75% reduction in coronary flow over 20 min. Filtration through a membrane of 0.8-micron porosity largely prevented this reduction of coronary flow. In studies with multidose cardioplegia (3-min infusions every 30 min), hearts given filtered solution recovered almost 90% of their preischemic functional capacity after 3 hr of hypothermic (20 degrees C) ischemic arrest. Hearts given an identical unfiltered solution essentially failed to recover despite the particle counts having conformed to the U.S.P. limit. This functional result was supported by measurement of creatine kinase leakage, which was significantly higher in the unfiltered group. These studies provide an argument for revision of U.S.P. particle limits when applied to intraarterially administered solutions; in particular, we believe that equipment for cardioplegic infusion into coronary arteries should incorporate a 0.8-micron in-line filter.

Animals↗
PubMedDate not supplied

[Surgical correction of acute congenital cardiopathies in the newborn infant].

The experience of the Cardiac Surgery Service at the Hospital del Niño IMAN with the deep hypothermia method and hemodynamic arrest is shown in 30 infants with severe congenital cardiac malformations. The procedures followed before and during the operation are carefully described in their three aspects; anesthesia, extracorporeal circulation and surgery, including postoperative care. Ventilatory assistance is stressed. Results are analyzed considering postoperative evolution; stress is made on the causes of morbidity and mortality. Considering the results of this and other similar reports, we believe that the deep hypothermia method and heart arrest in treating severe cardiac malformations in infants are of outstanding importance since they have significantly improved results in these problems.

Anesthesia, General↗
PubMed1995

Isotonic versus hypertonic initial hyperkalemic reperfusion after cardioplegic arrest in isolated hearts.

In 24 isolated perfused guinea-pig hearts, 40 min of hyperkalemic arrest and ischemia at 37 degrees C were followed by 5 min of either isotonic or hypertonic initial hyperkalemic reperfusion (HKR). Hearts were divided into 3 groups: HKR, 5 min initial reperfusion with isotonic hyperkalemic Krebs' solution; Mannitol, initial reperfusion with hypertonic (450 mosm für 1 min and 330 mosm for 4 more min) hyperkalemic Krebs' solution modified by addition of mannitol; NaCl, same as Mannitol group but using NaCl instead of mannitol to increase osmolarity. In isotonic HKR hearts, postischemic peak reflow was 98 +/- 11% of pre-ischemic control. Subsequently coronary flow stabilized at 75% of control. Left-ventricular developed pressure (LVDP) recovered to 60% of control. Hypertonic reperfusion increased peak reflow to 141 +/- 11% in the mannitol and to 121 +/- 12% in the NaCl groups, but had no effect on the subsequent reduction of coronary flow to 75% of control. Recovery of LVDP, dP/dtmax, dP/dtmin, the time constant of relaxation, and O2 consumption did not differ between groups. Postischemic flow responses to adenosine, acetylcholine, and nitroprusside were equivalently reduced in all groups. We conclude that the flow increase seen in the hypertonic reperfusion model of the study may be due to direct coronary vasodilation rather than the desired reduction of endothelial or perivascular cell edema by the hypertonic solutions.

Animals↗
PubMed2000

Coronary Surgery: off-pump and port access.

Attempts to minimize the invasiveness of cardiac surgery have focused on decreasing access trauma and eliminating cardiopulmonary bypass. The initial procedures, minimally invasive direct coronary artery bypass (MIDCAB, limited access beating heart) and port access (limited access arrested heart), have become niche procedures. Off-pump coronary artery bypass (OPCAB, median sternotomy beating heart) presently accounts for approximately 15% of all coronary bypass operations performed in the United States. Morbidity and cost appear to be decreased with these procedures. Feasibility trials of endoscopic coronary bypass surgery using robotic devices are underway in many centers. It is anticipated that over the next 5 years the alternative approaches to conventional coronary artery bypass surgery will continue to grow as methods of coronary revascularization.

Coronary Artery Bypass↗
PubMedDate not supplied

Imidazole action on guinea pig heart.

Imidazole (IM) exerts a positive inotropic effect on the guinea pig heart in a dose-dependent manner. This effect is not controlled by any of histamine receptors. Both, mepyramine - a H1-histamine receptor blocker, and cimetidine - a H2-histamine receptor blocker have no influence on IM responses. A positive inotropic action of IM on the heart has been shown in both, normal Ringer-Locke solution and in solutions with calcium deficit, however, the relative increase in contraction amplitude was higher at lower calcium concentrations than in solutions with normal calcium content. In calcium - free solution IM produces a marked delay of heart arrest, but fails to restore the heart action stopped by absence of calcium in the perfusion medium. The effects of IM and theophylline are additive. It is concluded that the action of IM on the guinea pig heart is not connected with histamine receptors, and a possible role of IM as a regulator of free calcium ions is suggested.

Animals↗
PubMed1987

Glutamate-blood cardioplegia improves ATP preservation in human myocardium.

Two groups of patients subjected to radical correction of Fallot's tetrad and defects of interventricular septum were investigated to ascertain whether the addition of glutamic acid to blood cardioplegic perfusate could improve preservation of myocardial ATP during cardiac arrest. In the control group (17 patients) the myocardial protection was performed by repeated infusions of cold blood potassium cardioplegic solution; in the 2nd group (24 patients) cardioplegic perfusate containing glutamic acid (20 mmol/l) was used. Left ventricular biopsies were taken during the first minute after cross-clamping of the aorta and before the release of the aortic clamp to determine ATP, glutamate and lactate. The cross-clamping time averaged 32 min in both groups. In the patients of the control group the losses of ATP correlated with the decrease in glutamate during the clamping period. A maintenance of a higher myocardial glutamate content by glutamate-containing cardioplegic perfusate prevented ATP fall or increased its level in patients of the 2nd group. There was no significant difference in lactate levels between the two groups by the end of the cardiac arrest. We conclude that enrichment of blood cardioplegic solution by glutamic acid, which may act as a substrate for anaerobic energy production, provides more effective myocardial protection during ischemic heart arrest.

Adenosine Triphosphate↗
PubMed1989

[Digital thermo-coronary angiography--development and validation of the method in comparison with conventional cine-coronary angiography].

We describe the technique-thermal coronary angiography (TCA)-for real-time assessment of coronary anatomy and flow. The goal of this study was to compare thermal coronary angiography to cine coronary angiography and to validate its value for detecting stenoses. We studied the exposed LAD both in beating and arrested hearts in 11 open-chest pigs by TCA and cine angiography. We used an AGA 782 Thermovision system combined with a TIC 8000 digital image processor providing coronary images with 0.1-0.2 mm spatial and 0.1 degrees C thermal resolution, and a CFR x-ray system. The coronary arteries were catheterized via the right carotid artery, using standard 5F catheters. The thermal camera was focused at a 1m-distance to the heart surface and the x-ray was angled to LAO position. We performed simultaneous thermal and cine angiography using Angiovist 370 at different temperatures (10-40 degrees C) and injection rates (1-2.5 ml/s). Different grades of stenoses were created by snares. Thermistor probe readings of the epimyocardium and the left atrial blood were performed to reference the thermal camera measurements. We obtained high resolution TCA images of both the coronaries and of the myocardial perfusion beds whenever there was greater than 4 degrees C difference between injectate and epicardial temperature. The TCA detection of stenoses as compared to cine angiography was 29/30 (96.6%) in arrested and 36/42 (85.7%) in beating hearts. Coronary occlusion produced immediate and dramatic perfusion defects as detected by TCA. TCAs were highly reproducible. Injection rate of 2 ml/s provided optimal thermal coronary images. Thermal angiograms of the LAD were sometimes affected by large crossing coronary veins, myocardial bridges, and excess of fat pretending nonexistent coronary stenosis. TCA is a highly sensitive and reproducible method as compared to standard coronary angiography and allows for detection of coronary stenoses. The image quality was best in arrested hearts.

Animals↗
PubMed2005

Vasopressin in cardiac arrest.

OBJECTIVE: To review the efficacy and safety of vasopressin in cardiac arrest. DATA SOURCES: MEDLINE, EMBASE, and PubMed were searched (all to June 2005) for full-text English-language publications describing trials in humans. Search terms were vasopressin, epinephrine, adrenaline, heart arrest, cardiac arrest, and clinical trial. STUDY SELECTION AND DATA EXTRACTION: Prospective, randomized, controlled trials that evaluated efficacy or safety endpoints of vasopressin in the management of cardiac arrest were included. Efficacy outcomes included return of spontaneous circulation, successful resuscitation, survival to hospital admission, 24-hour survival, and survival to hospital discharge. Safety outcomes were as defined by each trial. DATA SYNTHESIS: Three prospective trials were identified and included in this review. Vasopressin does not appear to offer any therapeutic advantage compared with epinephrine in the treatment of both in-hospital and out-of-hospital cardiac arrest, regardless of the presenting arrest rhythm. Although there is a suggestion that vasopressin may be effective in treatment of asystole, the evidence for this arises from a subgroup analysis that should be viewed as hypothesis generating. There are limited data describing the safety of vasopressin in cardiac arrest. CONCLUSIONS: The current evidence for the use of vasopressin in cardiac arrest is indeterminate. Given the similarly equivocal evidence of efficacy for epinephrine, either drug could be considered the first-line agent in cardiac arrest. Placebo-controlled studies with appropriate statistical power are warranted to evaluate meaningful clinical outcomes, such as survival to hospital discharge. Further evaluation of the role of vasopressin in asystolic cardiac arrest and its use in combination with epinephrine is also justified.

Clinical Trials as Topic↗
PubMed1997

Minimally invasive coronary artery bypass: a series with early qualitative angiographic follow-up.

BACKGROUND: Notwithstanding the advantages offered by minimally invasive coronary bypass, valid concerns have been raised about the technical accuracy of the distal anastomoses that can be fashioned on a beating heart. The main objective of our study was to undertake early and complete qualitative angiographic graft analysis in all patients undergoing this procedure. METHODS: All enrolled patients (25) from January to October 1996 who had bypass done by one surgeon via left minithoracotomy (19) or median sternotomy (6) on a beating heart underwent postoperative angiography within 4 to 6 hours. These angiograms were then reviewed for qualitative analysis and compared with a similar series done under conventional cardioplegic arrest. RESULTS: There was 97.5% graft patency (28/29) and no anastomotic occlusions. One internal thoracic artery was damaged. There was no mortality and no perioperative myocardial infarctions. All patients are alive and symptom free. The follow-up is 100% complete and ranges from 15 days to 11 months. Of the 26 anastomoses that could be assessed, 21 (81%) were grade A and 5 (19%) were grade B. In comparison, 24/25 (96%) of the anastomoses fashioned on an arrested heart by the same surgeon were grade A (p = 0.175). CONCLUSIONS: Minimally invasive coronary bypass can be carried out effectively and safely in a select group of patients, and the development of stabilizing devices and proper instrumentation should further improve results.

Anastomosis, Surgical↗