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Biomedical subjects

M Chiavarelli

Publications and source records attributed to M Chiavarelli.

At least 19 recordsLinked to original sources
PubMed1997

Cardiac binding in experimental heart failure.

BACKGROUND: Cardiomyoplasty is a potential therapy for heart failure. Its benefits are attributed to systolic augmentation (dynamic cardiomyoplasty) and prevention of cardiac dilatation (static cardiomyoplasty). To evaluate the static component, we used an artificial membrane for cardiac binding in a canine model of heart failure. METHODS: Intracoronary doxorubicin was administered weekly for 4 weeks to induce heart failure in 10 dogs, each of which was assigned to one of two treatment groups: (1) no treatment, or (2) cardiac binding. Hemodynamic data were obtained at operation and at 7 weeks after operation. Echocardiography was performed weekly. RESULTS: Left ventricular end-diastolic pressure and diameter, and right ventricular end-diastolic diameter increased in group 1 (from 9.6 +/- 6.1 to 19.6 +/- 2.3 mm Hg, p = 0.009; from 3.9 +/- 0.4 to 5 +/- 0.3 cm, p = 0.0013; and from 1.6 +/- 0.2 to 1.9 +/- 0.3 cm, p = 0.0036, respectively). Ejection fraction fell in group 1 from 0.60 +/- 0.10 to 0.40 +/- 0.04 (p = 0.0009) and in group 2 from 0.56 +/- 0.02 to 0.40 +/- 0.04 (p = 0.0001), but the difference between groups was not significant. CONCLUSION: Cardiac binding reduces the ventricular dilatation associated with heart failure without exacerbating left ventricular dysfunction.

Animals↗
PubMed1996

Nitric oxide-dependent and -independent modulation of sympathetic vasoconstriction in the human saphenous vein.

The possible modulation by the endothelium of the contractile responses to sympathetic nerve stimulation was examined in isolated superfused human saphenous vein. Contractile response curves for transmural nerve stimulation and noradrenaline were higher in endothelium-denuded than in intact human saphenous vein rings. In vessels with endothelium, transmural nerve stimulation- and noradrenaline-induced contractions were unaffected by the cyclooxygenase inhibitor, indomethacin (10 microM), but were potentiated by the nitric oxide (NO) synthase inhibitor, L-N omega-nitro-L-arginine (L-NNA, 3 microM) even when combined with D-arginine (0.3 mM), but not with L-arginine (0.3 mM). As in the case of noradrenaline, contractile responses to 5-HT, but not to KCI, were enhanced by endothelium removal, L-NNA or L-NNA plus D-arginine, but were unaffected by L-NNA plus L-arginine. The guanylyl cyclase inhibitor, methylene blue (10 microM), potentiated both transmural nerve stimulation- and noradrenaline-induced contractions in endothelium intact rings, whereas it enhanced, although to a lesser degree, only the neurally evoked contractions in endothelium-denuded human saphenous vein. In the vessels without endothelium L-NNA failed to affect the vasoconstriction induced by both transmural nerve stimulation and noradrenaline. Our results suggest that at least two inhibitory factors are involved in modulating the sympathetic vasoconstriction in the human saphenous vein: (1) at a postjunctional level, NO, the release of which from endothelial cells is probably stimulated by the activation of specific receptors, and (2) at a prejunctional level, an unidentified vasodilator agent, which is unmasked by the removal of the endothelium layer and which is probably co-released along with noradrenaline, and which acts through the guanylyl cyclase pathway.

Dose-Response Relationship, Drug↗
PubMed1996

Activation of creatine kinase-B and phospholamban gene expression in transformed latissimus dorsi muscle: evaluation of mRNA by polymerase chain reaction.

Latissimus dorsi muscle (LDM) transformation following chronic stimulation is the critical requirement for its use in cardiac assist procedures. In order to identify one or two molecular markers that can be used to effectively monitor the LDM transformation, the modulation in the expression of creatine kinase (CK) and phospholamban (PLB) genes by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was examined. Continuous in situ stimulation of left LDM was performed in four dogs for a period of 10 weeks after a vascular delay period of 2 weeks following surgery. For RT-PCR, gene-specific radiolabeled primers and equal amounts of cDNA synthesized from total RNA extracted from the LDM biopsies obtained at 4, 7, and 10 weeks of stimulation were used. A 2.6-fold increase in creatine kinase (brain type) (CK-B) mRNA was observed at transformed LDM compared to the control (P = 0.004) following 10 weeks of stimulation. On the contrary, a 30% decline was observed in creatine kinase (muscle type) (CK-M) mRNA level. An increase up to eight-fold was also observed in PLB mRNA in stimulated LDM compared to the contralateral muscle (P = 0.002). The PLB mRNA level in transformed LDM reached plateau and became comparable to that of normal heart after 7 weeks of stimulation. However, a sustained increase in CK-B mRNA level was observed until 10 weeks of stimulation. The level of beta-actin mRNA used as control remained the same in both stimulated and control samples. Thus the increase in CK-B and PLB mRNA and downregulation of CK-M mRNA in transformed LDM, demonstrated here by RT-PCR, indicate a switch from anaerobic to aerobic potential of transformed LDM along with a change towards slow-twitch phenotype and provide valuable markers to monitor the effectiveness of muscle transformation in cardiomyoplasty.

Actins↗
PubMed1994

In-vitro effects of cardioplegic solutions on human saphenous vein endothelium--a scanning electron microscopy study.

In order to evaluate the effects of potassium cristalloid cardioplegic solutions (CPS) on the endothelial morphology, human saphenous veins were studied by scanning electron microscopy after exposure to three CPS named MKP (magnesium-potassium-procaine cardioplegia), LK (low-potassium cardioplegia), and HKA (high-potassium-albumin cardioplegia) and to their main components. Vein rings, selected from the saphenous veins sampled for graft harvesting in 63 patients undergoing aorto-coronary bypass surgery, were exposed for 30, 60, and 120 minutes to the following buffered solutions: Krebs bicarbonate (as control); MKP cardioplegia; KCl (16.0 mmol/L); MgCl2(2).6H2O (16.0 mmol/L); Procaine (0.05 mmol/L); NaCl (92.5 mmol/L); LK cardioplegia; KCl (10.0 mmol/L); Mannitol (74.3 mmol/L); Glucose (27.7 mmol/L); HKA cardioplegia; KCl (30 mmol/L). Severe endothelial lesions, consisting of diffuse disendothelialization and diffuse signs of endothelial suffering, were induced by KCl (30 and 16 mmol/L) after 60-120 min, and by MKP cardioplegia and KCl (10 mmol/L) after 120 min. Moderate endothelial lesions, characterised by diffuse endothelial surface changes and focal cellular loss, were induced by KCl (30 and 16 mmol/L) after 30 min, MKP cardioplegia and KCl (10 mmol) 30-60 min, LK cardioplegia, HKA cardioplegia, and MgCl2.6H2O after 120 min. Slight endothelial lesions, consisting of diffuse endothelial bulging, or absence of significant endothelial changes, were found in samples otherwise treated. Our findings showed a significant damaging effect of CPS on the human saphenous vein endothelium in-vitro. The endothelial lesions seemed related to the presence of potassium and magnesium, and to prolongation of the time of exposure to the cardioplegic solutions.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardioplegic Solutions↗
PubMed1993

Evidence for sympathetic neurotransmission through presynaptic N-type calcium channels in human saphenous vein.

1. The specific type(s) of voltage-sensitive calcium channels (VSCCs) involved in sympathetic neurotransmission have not yet been characterized in human vascular tissues. We therefore examined the functional role of the N- and L-type VSCCs in human saphenous veins. 2. Contractile response curves for transmural nerve stimulation (TNS) and for exogenously administered noradrenaline (NA) were obtained in superfused saphenous vein rings. The contractions induced by TNS, but not by NA, were inhibited by 1 microM tetrodotoxin and by 10 microM guanethidine. Both responses were substantially reduced by 1 microM phentolamine, indicating that the contractions evoked by TNS were mediated by endogenous NA released from noradrenergic nerves. 3. In the presence of 2 microM omega-conotoxin GVIA (omega Conus Geographus toxin, fraction VI A; omega-CgTx), a polypeptide with specific inhibitory activity on N- and L-type calcium channels, the neurally evoked contractions were almost completely abolished. In contrast, the responses induced by exogenous NA were not affected by the neurotoxin, thus providing evidence of the exclusive presynaptic action of omega-CgTx. 4. In the presence of the calcium antagonist verapamil (10 microM), which selectively blocks L-type VSCCs, the contractions induced by both TNS and NA were diminished to the same extent, suggesting that the organic calcium blocker is active only at the postjunctional level. 5. It is concluded that N-type calcium channels are the main pathway of calcium entry controlling the functional responses induced by activating sympathetic nerves; the role of L-type channels appears to be limited to the postjunctional level, modulating smooth muscle contractions.

Adult↗
PubMed1993

Bless the babies: one hundred fifteen late survivors of heart transplantation during the first year of life. The Loma Linda University Pediatric Heart Transplant Group.

There is a rapid growth of interest in heart transplantation therapy during early infancy. From 10% to 25% of the infants who are listed for transplantation annually have died while awaiting a donor heart. There has been no significant trend in this variable. Since November 1985, 140 consecutive orthotopic transplantation procedures were performed in 139 infants who were from 3 hours to 12 months of age. Indications for transplantation included hypoplastic left heart syndrome (63%), other complex structural anomalies (29%), myopathy (6.5%), and tumors (1.5%). Most recipients had ductus-dependent circulation and received continuous infusion of prostaglandin E1. Heart donors were usually victims of trauma, sudden infant death, or birth asphyxia. A donor-recipient weight ratio of 4.0 or less was found to be acceptable. The amount of time the graft underwent cold ischemia, ranged from 64 to 576 minutes. The procurement process was facilitated by a single dose of cold crystalloid cardioplegic solution and cold immersion transport. Profound hypothermic circulatory arrest was used for graft implantation. One hundred twenty-four (89%) recipients survived transplantation and were discharged from the hospital. There were 9 late deaths, which resulted in an 83% overall survival. The 5-year actuarial survival is 80%. The survival among newborn recipients (n = 60) at 5 years is 84%. Chronic immunomodulation was cyclosporine-based and steroid-free. Surveillance was noninvasive and relied heavily on echocardiography, electrocardiography, and clinical intuition. There was one documented late lethal infection, tumor was not encountered, and coronary occlusive disease was known to exist in only one long-term survivor. We concluded that transplantation results in excellent life quality and is a highly effective and durable therapy when applied during early infancy.

Actuarial Analysis↗
PubMed1992

Neonatal cardiac transplantation. Intermediate-term results and incidence of rejection. Loma Linda University Pediatric Heart Transplant Group.

Early age at cardiac transplantation may favor successful engrafting with minimal chronic immunosuppression. Fifty-two newborns underwent orthotopic heart transplantation; 47 (90%) survived the operation, and 44 (85%) were late survivors. Actuarial survival was 92% at 1 month, 86% at 1 year, and 84% at 5 years. Forty-four infants who survived 12 weeks and the corresponding 100 rejection episodes were analyzed. Mean follow-up was 2.2 years. The mean number of rejections per year of follow-up was 1.2. No episodes of rejection were identified in six patients. Seven patients had a late rejection episode more than 1 year after transplantation, and only one had a late rejection episode after 2 years. Neonatal cardiac transplantation is effective and durable therapy for uncorrectable heart disease. Intermediate-term results are excellent. Severe rejection is uncommon, and few episodes occur after 1 year of follow-up.

Azathioprine↗
PubMed1992

Effects of cardioplegic solutions and their components on human saphenous vein contractility.

Cardioplegic solution administration into the vein graft is an established method to ensure cardioplegic distribution beyond coronary artery stenoses. The ultrastructural demonstration of severe endothelial damage after cardioplegic exposure suggests that intravenous cardioplegic administration can contribute to early and late graft thrombosis. The direct effect on human saphenous vein contractility of three cardioplegic solutions and their components was compared. A solution with 30 mmol/L K+ and 82 mmol/L Na+ produced intense venoconstriction. Lowering the potassium level to 10 mmol/L and increasing the sodium level to 92 mmol/L reduced its vasoconstricting action. A third solution with 16 mmol/L K+, 16 mmol/L Mg2+, and lidocaine caused venodilatation. Analysis of the single component effects showed that high potassium level, low sodium level, and the addition of lidocaine produced concentration-dependent vasoconstriction. High magnesium concentration resulted in vasodilatation. The present data suggest that cardioplegic solution composition may cause marked vasomotor effects on saphenous vein and thus influence its endothelial integrity. In the search for an "ideal solution" to the cardioplegic controversy, a venoconstrictor infusate should be avoided to improve patency rates of coronary artery bypass grafts.

Cardioplegic Solutions↗
PubMed1992

Arterial correction of double-outlet left ventricule by pulmonary artery translocation.

Double-outlet left ventricle is conventionally repaired with an intraventricular tunnel or with an extracardiac conduit when pulmonary stenosis is present. We report a 4-month-old female infant whose surgical correction of double-outlet left ventricle and subpulmonic stenosis was accomplished by pulmonary arterial translocation to the blind right ventricular infundibulum. This approach provided excellent hemodynamic repair without the use of an extracardiac conduit.

Double Outlet Right Ventricle↗
PubMed1991

[THe surgical treatment of aneurysmatic lesions of the ascending aorta: the immediate and long-term results in 40 patients].

From January 1981 to January 1991, 40 patients underwent operation for acute ascending aorta dissection (AAD, 14 patients), chronic ascending aorta dissection (CAD, 9 patients) or aortic ectasia (AE, 17 patients), with simultaneous aortic valve replacement in 30 cases (75%). Average age was 54 years with a 3:1 M/F ratio. In 20 cases (50%) a composite graft bearing a mechanical bileaflet valve was inserted with coronary artery reattachment (Bentall operation). In 16 cases (40%) the ascending aorta was replaced by a woven dacron graft alone (7 cases) or associated with aortic valve substitution (7 cases) or resuspension (2 cases). In 1 case (2.5%) a sutureless ring graft replacement of ascending aorta was carried out and 3 patients (7.5%) underwent aortoplasty with aortic valve substitution. Postoperative mortality rate was 21% for AAD group, 11% for CAD group and 6% for AE group. Non-fatal postoperative complications developed in 36% of AAD patients and in 78% and 29% of CAD and AE patients respectively. These complications occurred in 45% of patients who underwent Bentall operation, in 44% of those who underwent ascending aorta replacement associated with aortic substitution or resuspension, and in 14% of those operated of simple ascending aorta replacement. Average follow-up was 41.6 months (range 1.7-107.4 months). During this period 5 deaths occurred for a long-term mortality rate of 14.2%. Out of 30 survivors 21 (70%) underwent CT-study to evaluate the natural course of the false channel and the risk of redissection or late aneurysm formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Ultrastructural changes of coronary artery endothelium induced by cardioplegic solutions.

Coronary artery endothelial and myocardial ultrastructure was studied in guinea-pig heart-lung preparations (HLP) subjected to ischemic cardiac arrest induced by three hypothermic solutions. Two of the solutions used had high potassium chloride concentration ("Alabama" and "St. Thomas") while the third, instead, was a bicarbonate buffer (Kreb's solution). Five experimental groups were studied. In group 1 (control) the HLP were not subjected to cardiac arrest. Groups 2, 3, and 4 were subjected to a period of cardiac arrest of 30, 60, and 120 minutes respectively. In group 5, HLP were reperfused with blood for 30 minutes after 60 minutes of cardiac arrest. A thin ring of the left anterior descending coronary artery and myocardial fragments were obtained at the end of each experiment and were analyzed by means of transmission electron microscopy (TEM). Functional parameters were recorded in group 5. HLP perfused with Alabama solution showed a well-preserved endothelium and myocardium. HLP perfused with Krebs solution showed slight changes of the endothelial glycocalix only in group 4. Further, HLP perfused with Krebs solution showed extensive myocardial lesions (groups 3 and 4). These ischemic changes were not completely reversed after reperfusion (group 5). HLP perfused with St. Thomas solution showed only endothelial changes. These lesions were mainly characterized by: disappearance of the glycocalix and pynocytotic vesicles, endothelial cell bulging (group 2), and loss of the endothelial continuity (groups 3, 4, and 5). Hemodynamic parameters were significantly changed only in the Krebs-perfused HLP which showed a deterioration of the cardiac function related to the ischemic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The influence of positive end-expiratory pressure on intrapericardial pressure and cardiac function after coronary artery bypass surgery.

The hemodynamic effects of positive end-expiratory pressure (PEEP) were studied in coronary artery bypass patients by recording intrapericardial and intracardiac pressures, measuring cardiac output by thermodilution, and determining left ventricular volumes by nuclear radiography. An elevation of PEEP to 5, 10, and 15 cm H2O led to a decrease in cardiac output (15% decrease at PEEP 15) as intrapericardial pressure increased and transmural left atrial pressure decreased. Modest volume loading (an increase in left atrial pressure of 3 mm Hg) greatly attenuated the deleterious effects of 15 cm H2O PEEP. There was an excellent correlation between pulmonary capillary wedge pressure and left atrial pressure at PEEP 0 and 5 (r = .85 and r = .83). This correlation was not nearly as reliable at PEEP 15 (r = .54). A predictable increase in intrapericardial pressure was observed as PEEP was applied in these patients. The magnitude of this increase can be estimated by multiplying the change in PEEP (in cm H2O) by 0.4 to estimate the change in intrapericardial pressure (in mm Hg). Using this estimation as a guide, modest volume loading can be used to maintain transmural filling pressures (and cardiac output) when PEEP is used after coronary artery bypass surgery.

Coronary Artery Bypass↗
PubMed1987

Right ventricular outflow construction without cardiopulmonary bypass.

Establishment of right ventricular-pulmonary arterial continuity without the use of cardiopulmonary bypass was undertaken in 36 patients with different anomalies associated with pulmonary atresia or severe stenosis. Hospital mortality was 11% with no late death. Fourteen of the 27 individuals with pulmonary atresia, ventricular septal defect, and hypoplastic confluent pulmonary arteries had adequate angiographic follow-up, which demonstrated significant pulmonary artery enlargement. Five patients underwent total correction, two after unifocalization operations to establish lobar pulmonary arterial continuity. Symmetric growth of the left and right pulmonary artery was not achieved. However, the enlargement was adequate for potential final repair in all the patients with an unrestricted outflow tract.

Blood Vessel Prosthesis↗
PubMed1987

Modifications of the Fontan operation applicable to patients with left atrioventricular valve atresia or single atrioventricular valve.

Two modifications of the Fontan operation are proposed for prevention of pulmonary venous obstruction in patients with left atrioventricular valve atresia or single atrioventricular valve. In the first technique, a bipedicled flap of right atrial wall is used to separate systemic and pulmonary venous drainages; an atriopulmonary connection is constructed by use of the right atrial appendage, and the defect in the right atrial wall is repaired with a pericardial patch. In the second technique, the superior vena cava is transected and the cardiac and cephalad ends are anastomosed separately to the pulmonary arterial confluence. A patch is positioned inside the right atrium to separate the systemic from the pulmonary venous drainage. Both techniques achieve unrestricted systemic and pulmonary venous channels. Severe atrial arrhythmias, present in the four patients operated on with the first procedure, were not seen in 12 patients who had repair with the second procedure.

Heart Atria↗
PubMed1986

Calcium entry blockers and cardioplegia: interaction between nifedipine, potassium, and hypothermia.

The potential additive protective effect provided by nifedipine to the University of Alabama Hospitals cardioplegia solution (ACS) was assessed with the use of a guinea pig heart-lung model of cardiopulmonary bypass and ischemic arrest. The addition of nifedipine consistently enhanced the protective properties of ACS infused at 37 degrees C; functional recovery was similar to that observed with cold ACS. Despite the additional protection under normothermic conditions, nifedipine did not improve recovery after infusion at 4 degrees C. The abolition by hypothermia of the protective effects of nifedipine suggests a similarity in action between nifedipine and hypothermic protection. The interaction between ACS and nifedipine was studied on bovine coronary arteries in vitro. Nifedipine caused a marked reduction in the coronary vasoconstricting effect of ACS, both under normothermic and hypothermic conditions. The use of nifedipine in cardioplegia may provide additional protection when uneven distribution of the cardioplegic solution is expected and hypothermic protection is unreliable.

Animals↗
PubMed1985

Interactions between pharmacological cardioplegia and hypothermia for intraoperative myocardial protection.

Cold cardioplegia is currently the method of choice for providing myocardial protection during open-heart surgical procedures. Two components of protection, perfusion cooling and pharmacological cardiac arrest, were investigated in the guinea pig heart-lung model. The effects of two cardioplegic solutions, the University of Alabama Hospital solution and the St. Thomas' Hospital solution, and a control perfusate were compared. The results confirmed the efficacy of hypothermia as a protective agent and the additional protection afforded by pharmacological cardioplegia. Infusion temperature critically influenced the cardioprotective action of the Alabama solution: Striking protection was afforded only under hypothermic conditions, whereas myocardial damage was exacerbated by the infusion at 37 degrees C. The St. Thomas' Hospital solution provided substantial protection independent of infusion temperature. Thus, the safety margin of the Alabama solution was narrower than that of the St. Thomas' solution. It is suggested that the difference between the two cardioplegic solutions partially depends on their coronary vasoactivity, since the administration of the Alabama solution at 37 degrees C increased coronary perfusion pressure. It would seem worthwhile to use a temperature-independent cardioplegic solution devoid of coronary vasoconstricting action.

Animals↗