Jiang Gu

Preservation of the Latissimus Dorsi Muscle During Cardiomyoplasty Surgery

Abstract Background: Cardiomyoplasty surgery has been shown to be associated with damage and degeneration of the assisting skeletal muscle. The purpose of this study was to use ischemic (short‐term) and thermal (long‐term) preconditioning to protect the muscle during surgery and the subsequent ischemia. Methods: Three 10‐minute cycles of ischemia‐reperfusion were accomplished noninvasively on goat latissimus dorsi muscle (LDM) immediately prior to surgery. In another experiment, LDM was noninvasively heat shocked for 20 minutes at 42°C 24 hours prior to surgery. LDM damage was evaluated 5 days postsurgery using enzyme activities (β‐glucuronidase, β‐GLN; citrate synthase), hydroxyproline, morphology, and blood flow. Results: The lysosomal enzyme, β‐GLN, was significantly increased (43%, p < 0.05) by surgical dissection and remained high in the ischemic preconditioned LDM (58%, p < 0.05) and in the heat shocked LDM (57%, p < 0.05). Conclusion: These findings show that these two protective protocols do not reduce the muscle damage that occurs during surgical preparation of the LDM for cardiomyoplasty.

Effectiveness of Fibrin Glue in the Reduction of Postoperative Intrapericardial Adhesions

The hemostatic properties of fibrin sealant have been well described. Previously published reports have attempted to clarify the possible role of fibrin glue in the inhibition of the formation of intrapericardial adhesions following cardiac surgery. Earlier work hypothesized that fibrin glue may reduce the severity of postoperative adhesions and that the use of autologous fibrin glue may have similar effects, without the risks that accompany homologous blood products. Six juvenile farm pigs were utilized to test this hypothesis. Conventional fibrin glue and single-donor fibrin glue were tested in open-heart surgery. This experimental model was also reexamined and found to be of significant utility in simulating adult reoperative cardiac surgery. The fibrin glue subjects were universally easier to reoperate due to fewer adhesions, as demonstrated grossly and histologically. The single-donor fibrin glue had no significant advantage on adhesion formation, when compared to the conventional fibrin glue group, but the ramifications of formulating fibrin glue in this fashion offer a significant benefit toward the complete use of autologous blood products in open-heart surgery.

Physical Overdistension Converts Ventricular Cardiomyocytes to Acquire Endocrine Property and Regulate Ventricular Atrial Natriuretic Peptide Production

Atrial natriuretic peptide (ANP) is present in adult atria but at very low concentrations in normal adult mamma lian ventricles. In the atria, the produc tion of ANP is regulated by physical distension of the atrial wall. The same phenomenon was investigated in the ventricles of rats and men. Cardiac tis sues from human ventricular aneurysm (n = 5), spontaneously hypertensive rats (n = 30), and rats that had overloaded left ventricles induced by surgery (n = 84) were studied with the methods of light microscopic immunocytochemis try, electron microscopic immunogold staining, and RNA-RNA tissue in situ hybridization. It was found that the levels of ANP gene expression, ANP im munoreactivity, and ANP-containing specific granules in the overburdened ventricles were elevated and their de grees of fluctuation were directly pro portional to the force of physical dis tension applied to the ventricular car diomyocytes. In rats, ANP mRNA and ANP immunoreactivity returned to the control level seven days after the ventri cular overload was surgically released. The changes of ANP and its mRNA in the ventricles were related more closely to the changes of intraventricular pres sure than to cardiocytic hypertrophy. In addition, ANP immunoreactivity was demonstrated in Purkinje cells and peri arteriolar cardiomyocytes in the ventri cles of normotensive rats. In conclusion, physical overstretch of the ventricle wall is likely to be the triggering factor affect ing ventricular cardiomyocytes to ac quire endocrine property, and also to regulate the production of ventricular ANP, thereby contributing to the con trol of the blood volume and the blood pressure.

Esmolol and percutaneous cardiopulmonary bypass enhance myocardial salvage during ischemia in a dog model

Despite recent advances in techniques of reperfusion for acute myocardial ischemia, myocardial salvage remains suboptimal. Beta-blockers have been shown to limit infarct size during acute ischemia, but their negative inotropic properties have limited their use. Cardiopulmonary bypass is an attractive technique for cardiac resuscitation because it can stabilize a hemodynamically compromised patient and potentially reduce myocardial oxygen consumption. In an attempt to maximize myocardial salvage in the setting of acute ischemia, the combination of esmolol, an ultrashort-acting beta-blocker, with percutaneous cardiopulmonary bypass was evaluated. Four groups of instrumented dogs underwent 2 hours of myocardial ischemia induced by occlusion of the proximal left anterior descending coronary artery, followed by 1 hour of reperfusion. Throughout the period of ischemia and reperfusion, esmolol plus percutaneous cardiopulmonary bypass was compared with esmolol alone, percutaneous cardiopulmonary bypass alone, and control conditions. After the reperfusion period, the extent of infarction of the left ventricle at risk was determined. Four animals had intractable arrhythmias: one in the esmolol plus bypass group, one in the esmolol group, and two in the control group. The extent of infarction of the left ventricle at risk was significantly reduced in the esmolol plus bypass group (30%) compared with bypass alone (52%), with esmolol alone (54%), and with the control groups (59%; p < 0.05). We conclude that in this experimental model the combination of esmolol with bypass improves myocardial salvage after ischemia and reperfusion.

Determination of infundibular innervation and amine receptor content in cyanotic and acyanotic myocardium: Relation to clinical events in tetralogy of Fallot

SummaryRight ventricular myocardium was assessed for cholinergic and adrenergic innervation, as well as alpha-adrenergic, beta-adrenergic, and muscarinic receptors, in 18 cyanotic patients with tetralogy of Fallot (TOF) and four acyanotic control patients with ventricular septal defect, each of whom underwent a cardiac repair from June through December 1987.Neurons containing acetylcholine (ACH), neuron-specific enolase (NSE), S-100 protein, neuropeptide-Y (NPY), dopamine-beta-hydroxylase (DBH), and calcitonin gene-related polypeptide (CGRP) were detected surrounding arterioles and myocytes in all specimens. NSE and S-100 immunoreactivities were also identified in the cytoplasm of TOF cardiocytes, possibly indicating a neuroendocrine origin of these cells. Cardiocyte size was increased in TOF (p=0.05). Acetylcholine (cholinergic) (p=0.04) and CGRP (cholinergic) positive neurons (p=0.07) were decreased in the TOF as compared to controls. Adrenergic fiber content (p=0.15) and beta receptors (p=0.21) were similar in both groups. There was an increase in muscarinic receptors in the controls (p=0.002), and a marked increase in alpha receptors in TOF (p=0.019). There were no intragroup differences in the TOF patients according to degree of cyanosis.In conclusion, there were important differences in neuronal and amine receptor content between TOF and control patients. Increased alpha receptors in TOF could account for differences in clinical and hemodynamic events.

Localized endocrine conversion of ventricular cardiocytes in ventricular aneurysm

Atrial natriuretic peptide (ANP) is synthesized and stored in the atria of the heart, but not or at very low concentrations in the ventricles. We investigated the occurrence of ANP and its messenger RNA (mRNA) in human ventricular aneurysm where the cardiocytes were physically over-stretched. The techniques of light and electron microscopic immunocytochemistry, and RNA-RNA tissue in situ hybridization were employed. A large amount of ANP immunoreactivity was found in the cytoplasm of the cardiocytes in and around the aneurysm, but not in fibrous scar tissue or in the normal ventricles. Immunoelectron microscopy localized the immunoreactivity mainly to specific secretory granules in the cytoplasm of the cardiocytes. ANP mRNA was also detected in these cardiocytes. The abundance of both was much higher than that found in the hypertrophic ventricles of other types. The highest concentration of ANP immunoreactivity and of ANP mRNA was found in the cardiocytes located at the border zone. The quantities of both ANP and its mRNA decreased in cardiocytes more distant from the lesion. Our findings suggest that human ventricular cardiocytes in and around aneurysm can convert to produce large amounts of the endocrine peptide ANP. This ventricular endocrine conversion was localized and was probably caused by physical over-stretch of the cardiocytes.

The Cryopreserved Stented Pulmonary Homograft Valve in the Tricuspid Position

Abstract This study was designed to evaluate the early phase events occurring in a stented pulmonary homograft valve implanted in the tricuspid position. A human pulmonary homograft was sterilized in antibiotic solution for 48 hours and cryopreserved in liquid nitrogen (–176°C). Following thawing and trimming, the pulmonary valve was mounted on a Dacron cloth‐covered Delrin stent and implanted into the tricuspid position in 3‐month‐old sheep, for a mean of 95 ± 5 days. Seven animals were studied. Morphological assessment indicated good structural tissue preservation despite a decrease in viable fibroblasts noted in the distal part of the leaflets. The collagen fibers remained unchanged, and no tissue calcification was found. Viability of the mounted homograft was evaluated using an in vitro tissue culture method, and the viable cells underwent chromosomal analysis to identify whether they originated from the donor or host. Cells with 56 chromosomes, a number intrinsic to sheep cells, were cultured from the donor‐recipient junctional area. Hemodynamic and angiographic data, which were collected at the time of both implantation and explantation, revealed no functional deterioration of the implanted valve over 3 months. At the time of explantation, six of the seven valves were competent and no cusp retraction or thickening was noted. The seventh valve had deteriorated due to endocarditis. We conclude that stented cryopreserved pulmonary homografts may be useful as bioprostheses in the tricuspid position.

Tracheal Homograft as Aortic Conduit: Early Phase Results

The aim of this study was to evaluate the performance of tracheal homografts as aortic conduits. Fourteen tracheal grafts freshly procured from rats were preserved by the following two methods: cryopreservation (n = 6) and treatment with glutaraldehyde 0.2 % (n = 8). The explanted tracheae were stored for ten to twenty days prior to implantation. They were subsequently implanted into the infrarenal aorta of the recipient rats. The average length replaced was 1 to 1.5 cm. The grafts were then evaluated after a period of one (n = 6, 2 cryopreserved, 4 gluteraldehyde), two (n = 4, 2 cryopreserved, 2 glutaraldehyde), and three (n = 4, 2 cryopreserved, 2 gluteraldehyde) weeks for their performance, morphol ogy, and histopathology. The rats did well postoperatively with adequate distal perfusion. Two of the 6 rats with cryopreserved grafts had reduced flow as evidenced by lack of pulsation in the aorta distal to the graft, and histologic examination revealed incompletely occluding thrombus adherent to the luminal surface. The remaining cyropreserved and glutaraldehyde-fixed grafts had good flow and did not show any radiologic evidence of narrowing at the site of anastomosis or in the region of the graft. Histopathologic examination showed that the glutaraldehyde-treated homografts had better morphology, intact carti lage, and no or mild inflammatory response. The cryopreserved tracheal homo grafts showed degenerative changes in the cartilage. The inflammatory response was moderate, and the mucosa was either ruptured or absent. In the 2 that had reduced flow, there was marked cartilage necrosis and inflammatory response with thrombus formation in the lumen. This early phase study shows that tracheal homografts functioned well as conduits in the aortic position and gluaraldehyde treated homografts have better morphology than cryopreserved homografts.

Results with Cryopreserved and Glutaraldehyde-Preserved Allograft Trachea as an Arterial Conduit

The authors evaluated rat tracheas as biological arterial conduits. Forty-eight Wistar rats were used; 24 received cryopreserved trachea (CT) and 24 received glutaraldehyde-treated trachea (CT). The homograft tracheas were procured from two-to-three-week old donor Wistar rats. The homograft tracheal grafts were implanted end-to-end in the infrarenal abdominal aorta. The mean aortic cross- clamp time was thirty-three minutes (range twenty-seven to forty minutes). Four animals from each group were evaluated and sacrificed at weeks 1,2,3,6,12, and 24 after implantation. At necropsy, hemodynamic, angiographic, and histopatho logic examinations were performed. In the CT group, 5 animals (20.8%) had aneurysmal changes in the graft, resulting in 2 sudden deaths. In the GT group, all grafts were patent, and there was no incidence of aneurysm formation or abnormal pressure gradients across the grafts. Histopathologic examinations showed that GT had much slower degeneration of the graft. The cross linking of collagen and slow degeneration of cartilage in GT allow time for fibroblastic proliferation to enhance integrity of GT, preventing aneurysm formation. The authors conclude that the structure and function of GT for six months were ex cellent and superior to those of CT and that GT may be useful as arterial grafts.

Physical Manipulation of Subcutaneously Implanted Cardiac Muscle in Rat Increased Plasma Atrial Natriuretic Peptide Concentration

To examine the effects of physical stretch on cardiac muscle endocrine activ ity, the authors transplanted whole neonatal hearts subcutaneously into the back and the ears of the correspondent mother (n=9). Seven days later, physical manipulation was applied on the implanted heart by stretching the skin and the subcutaneous tissue encasing the implanted cardiac muscle, for a period of five to ten minutes. Such manipulation was repeated approximately every seven days postoperatively for a total of two to four times for each rat. The plasma atrial natriuretic peptide (ANP) levels were measured by radioimmunoassay prior to and immediately following manipulation. Postmanipulation plasma ANP levels were found to increase from the premanipulation levels. At two weeks postimplant, the average increase was 290% with the highest single-speci men increase being nearly twelvefold. The increases observed at two and three weeks following implantation had Signed Rank Test p values of 0.015 and 0.042 respectively. The viability of the implanted hearts was confirmed by cell culture. Light microscopic immunocytochemistry detected ANP immunoreactivity in the implanted cardiocytes. The elevated plasma ANP concentration induced by the manipulation appeared to be correlated with the functional status of the im planted cardiocytes. In conclusion: (1) Subcutaneously transplanted neonatal myocardiocytes survived for at least three to four weeks while retaining the ability to produce ANP. (2) Physical manipulation of implanted heart induced ANP release. There fore, cardiac ANP production and release is indeed stimulated by physical stretching.