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Biomedical subjects

F M Lupinetti

Publications and source records attributed to F M Lupinetti.

At least 19 recordsLinked to original sources
PubMed1998

Temperature threshold and modulation of energy metabolism in the cardioplegic arrested rabbit heart.

Hypothermia protects ischemic tissues by reducing ATP utilization and accumulation of harmful metabolites. However, it also reduces ATP production, which might cause deterioration in the energy supply/demand ratio. Modulation of energy supply/demand according to temperature has not been previously studied in detail. In this study, isolated, perfused rabbit hearts (n = 60) were used to determine the effects of various temperatures on myocardial energy metabolism and function during cardioplegic arrest. Ischemia was induced by crystalloid cardioplegic solution at 4, 18, 30, and 34 degrees C for 120 min, respectively. At each temperature, the hearts were divided into a glucose-treated group which contained 22 mM glucose in cardioplegic solution as the only substrate and a control group which contained 22 mM mannitol to keep same osmolarity. Following 15 min reperfusion, recovery of left ventricular developed pressure (DP), +/- dP/dtmax, and the product of heart rate and DP were significantly higher in 30, 18, and 4 degrees C groups than those in 34 degrees C control group. The functional recovery was also significantly higher in the 34 degrees C glucose-treated group than that in the 34 degrees C control group, but there was no difference between those groups at 30 degrees C and the temperature below 30 degrees C. Myocardial ATP concentration was significantly lower in 34 degrees C control group than those in other groups. There is a close relationship between myocardial ATP concentration and functional recovery (R2 = 0.90). The accumulations of lactate and CO2 were significantly higher at 34 degrees C in glucose-treated group than those in the control group. However, there was no significant difference between these two groups at 30 degrees C and the temperature below 30 degrees C. These results indicate that under these study conditions: (1) a marked decrease in energy supply/demand occurs above 30 degrees C, implying that a temperature threshold exists; and (2) this can be ameliorated by provision of glucose as substrate in cardioplegia solution.

Adenosine Triphosphate↗
PubMed1998

Temperature threshold and preservation of signaling for mitochondrial membrane proteins during ischemia in rabbit heart.

Temperature modulates both myocardial energy requirements and production. We have previously demonstrated that myocardial protection induced by hypothermic adaptation preserves expression of genes regulating heat shock protein and the nuclear-encoded mitochondrial proteins, the adenine nucleotide translocator isoform 1 (ANT1), and the beta subunit of F1-ATPase (beta F1-ATPase). This preservation is associated with a reduction in ATP depletion similar to that noted in cardioplegic arrested hearts preserved at a critical temperature (30 degrees C) or below. We tested the hypothesis that expression of these genes may also be subject to this temperature threshold phenomenon. Isolated perfused rabbit hearts were subjected to ischemic cardioplegic arrest at 4, 30, or 34 degrees C for 120 min. Cardiac function indices and steady-state mRNA levels for ANT1, beta F1-ATPase, and HSP70-1 were measured prior to ischemia (B) and after 45 min of reperfusion. Cardiac function was significantly depressed in the 34 degrees C group. Ischemia at 34 degrees C reduced steady-state mRNA levels for ANT1 and beta F1-ATPase from B, but these levels were similarly preserved at 4 and 30 degrees C. HSP70-1 levels were mildly elevated (fourfold) above B to similar levels at all three temperatures. These results indicate that mRNA expression for ANT1 and beta F1-ATPase is specifically preserved in a pattern consistent with the temperature threshold phenomenon. HSP70-1 expression is not influenced by ischemic temperature. Preservation of gene expression for these mitochondrial proteins implies that signaling for mitochondrial biogenesis or resynthesis is maintained after ischemic insult.

Animals↗
PubMed1998

Hypothermia preserves function and signaling for mitochondrial biogenesis during subsequent ischemia.

Hypothermia is known to protect myocardium during ischemia, but its role in induction of a protective stress response before ischemia has not been evaluated. As cold incites stress responses in other tissues, including heat shock protein induction and signaling mitochondrial biogenesis, we postulated that hypothermia in perfused hearts would produce similar phenomena while reducing injury during subsequent ischemia. Studies were performed in isolated perfused rabbit hearts (n = 77): a control group (C) and a hypothermic group (H) subjected to decreasing infusate temperature from 37 to 31 degrees C over 20 min. Subsequent ischemia during cardioplegic arrest at 34 degrees C for 120 min was followed by reperfusion. At 15 min of reperfusion, recovery of left ventricular developed pressure (LVDP), maximum first derivative of left ventricular pressure (LV dP/dtmax), LV -dP/dtmax, and the product of heart rate and LVDP was significantly increased in H (P < 0.01) compared with C hearts. Ischemic contracture started later in H (97.5 +/- 3.6 min) than in C (67.3 +/- 3.3 min) hearts. Myocardial ATP preservation and repletion during ischemia and reperfusion were higher in H than in C hearts. mRNA levels of the nuclear-encoded mitochondrial proteins adenine nucleotide translocase isoform 1 (ANT1) and beta-F1-adenosine-triphosphatase (beta-F1-ATPase) normalized to 28S RNA decreased in C hearts but were preserved in H hearts after reperfusion. Inducible heat shock protein (HSP70-1) mRNA was elevated nearly 4-fold after ischemia in C hearts and 12-fold in H hearts. These data indicate that hypothermia preserves myocardial function and ATP stores during subsequent ischemia and reperfusion. Signaling for mitochondrial biogenesis indexed by ANT1 and beta-F1-ATPase mRNA levels is also preserved during a marked increase in HSP70-1 mRNA.

Adenine Nucleotides↗
PubMed1997

Comparison of human tissues and mechanical prostheses for aortic valve replacement in children.

BACKGROUND: Aortic valve replacement in children is problematic because of complications of mechanical valves and uncertain outcomes associated with human valves. The results of pediatric aortic valve replacements over 5 years were reviewed. METHODS AND RESULTS: Mechanical valves were used exclusively during the first part of this series (n = 26). Thereafter, 25 consecutive aortic valve replacements were performed with autografts (n = 19) or allografts (n = 6). Allografts were used for Marfan's syndrome patients or those with unusable pulmonary valves. Among autograft/allograft recipients, 16 patients underwent 27 prior operations. In the mechanical group, 18 patients underwent 19 previous operations. Three patients in each group underwent a previous mechanical aortic valve replacement. Operative complications included two mild strokes and one pacemaker in the autograft/allograft group and three deaths and two pacemakers in the mechanical group. One autograft recipient required reoperation for pulmonary allograft stenosis. In the mechanical group, late complications included six cases of nonstructural degeneration and two cases of endocarditis, with three reoperations. Reoperation-free survival was 96% at 2 years in the autograft/allograft group and 80% at 2 years and 75% at 3 years in the mechanical group. Event-free survival was 96% at 2 years in the autograft/allograft group compared with 67% at 2 years and 49% at 3 years in the mechanical group (P < .05). CONCLUSIONS: The frequency of reoperations for mechanical aortic valve replacement has been surprisingly high. Aortic valve replacement in children with only autografts or allografts achieves good early results.

Adolescent↗
PubMed1997

Influence of the pH of cardioplegic solutions on cellular energy metabolism and hydrogen ion flux during neonatal hypothermic circulatory arrest and reperfusion: a dynamic 31P nuclear magnetic resonance study in a pig model.

OBJECTIVES: The pH of cardioplegic solutions is postulated to affect myocardial protection during neonatal hypothermic circulatory arrest. Neither optimization of cardioplegic pH nor its influence on intracellular pH during hypothermic circulatory arrest has been previously studied in vivo. Thus we examined the effects of the pH of cardioplegic solutions on postischemic cardiac function in vivo, including two possible operative mechanisms: (1) reduction in adenosine triphosphate use and depletion of high-energy phosphate stores or (2) reduction of H+ flux during reperfusion, or both. METHODS: Dynamic 31P spectroscopy was used to measure rates of adenosine triphosphate use, high-energy phosphate depletion, cytosolic acidification during hypothermic circulatory arrest, and phosphocreatine repletion and realkalinization during reperfusion. Neonatal pigs in three groups (n = 8 each)--group A, acidic cardioplegia (pH = 6.8); group B, basic cardioplegia (pH = 7.8); and group N, no cardioplegia--underwent hypothermia at 20 degrees C with 60 minutes of hypothermic cardioplegia followed by reperfusion. RESULTS: Recoveries of peak elastance, stroke work, and diastolic stiffness were superior in group B. Indices of ischemic adenosine triphosphate use, initial phosphocreatine depletion rate, and tau, the exponential decay half-time, were not different among groups. Peak [H+] in group A (end-ischemia) was significantly elevated over that of group B. The realkalinization rate was reduced in group B compared with that in groups A (p = 0.015) and N (p = 0.035), with no difference between groups A and N (p = 0.3). Cytosolic realkalinization rate was markedly reduced and the half-time of [H+] decay was increased during reperfusion in group B. CONCLUSIONS: Superior postischemic cardiac function in group B is not related to alterations in ischemic adenosine triphosphate use or high-energy store depletion, but may be due to slowing in H+ efflux during reperfusion, which should reduce Ca++ and Na+ influx.

Adenosine Triphosphate↗
PubMed1997

Effect of cryopreservation and histocompatibility on type I procollagen gene expression in aortic valve grafts.

BACKGROUND: Allograft valves are excellent substitutes for diseased or absent valves but undergo primary tissue degeneration. Fibroblast viability may determine resistance to valve deterioration. This study evaluated gene expression for procollagen by valve grafts and studied the effects of cryopreservation and histocompatibility on this property. METHODS AND RESULTS: Fresh and cryopreserved rat aortic valves were implanted heterotopically into syngeneic or allogeneic recipients. Nonviable, cryothermally injured valves were used as negative controls. The grafts and native aortic roots were excised 3 days after implantation. Northern hybridization with a human procollagen alpha 1 (I) complementary DNA probe was used to assess the expression of type I procollagen mRNA. The content of procollagen mRNA relative to 18S ribosomal RNA was evaluated by means of scanning densitometry. In situ hybridization was used to locate the areas of procollagen mRNA expression in the grafts. Both fresh and cryopreserved grafts exhibited greater expression than the native valve. This increase in expression was observed in both syngeneic and allogeneic grafts, but not in the negative control group. In situ hybridization showed a strong signal for procollagen in the aortic wall and a weak signal in the leaflet and myocardium in the viable grafts and in native tissues. CONCLUSIONS: Regardless of preservation or allogenicity, fibroblast viability in aortic valve grafts persists after implantation. Increased gene expression for procollagen suggests a capacity for repair and regeneration.

Animals↗
PubMed1997

Procollagen production in fresh and cryopreserved aortic valve grafts.

Long-term durability of aortic valve allografts may be enhanced by cellular capacities for regeneration and repair. To evaluate aortic valve graft production of an important structural protein, rat aortic roots were implanted heterotopically into the abdominal aorta of recipient rats. Grafts were either syngeneic or strongly allogeneic, were implanted either fresh or after cryopreservation, and were left in place 2 to 21 days after implantation. A total of 80 aortic valve grafts and the corresponding native aortic valves were examined. The grafts were retrieved and immunocytochemically stained for the presence of procollagen, a precursor to collagen. Regardless of histocompatibility or preservation, grafts exhibited consistent procollagen presence that equaled or exceeded that seen in the corresponding native valves. Positive procollagen staining was predominantly in the aortic wall. The most prominent staining was near the hinge point of the valve leaflets, with no staining in the free portion of the leaflets. Staining with alpha-actin demonstrated vascular smooth muscle in sites remote from the areas positive for procollagen, which suggests that vascular smooth muscle was not responsible for the procollagen production. These findings indicate that cryopreservation is compatible with persistent fibroblast viability and in vivo protein synthesis by both syngeneic and allogeneic aortic valve grafts.

Animals↗
PubMed1996

Stent redilation in canine models of congenital heart disease: pulmonary artery stenosis and coarctation of the aorta.

In a canine puppy model, pulmonary artery stenosis was created by banding the left pulmonary artery to 30-40% of its original diameter. Animals underwent right heart catheterization and angiography 1-2 mo later, and Palmaz P308 stents were implanted. Stent redilation was performed 3-5 mo later. One mo postredilation, the animals were restudied and sacrificed. Coarctations of the aorta were created by transverse aortic incision and longitudinal repair. P308 stent implantation was performed 2-3 mo later. Stent redilation was performed after 6-10 mo, and the animals were restudied and sacrificed 1-2 mo later. Stent implantation was performed in 6 puppies with pulmonary artery stenosis, as 2 animals developed postoperative pulmonary arterial hypoplasia, precluding stenting. The stenosis diameter increased from 4.8 +/- 0.5 mm to 7.4 +/- 0.6 mm (mean +/- SE) following stenting (P = 0.005), and increased further to 9.2 +/- 0.7 mm following redilation (P < 0.001). There were no significant vessel tears or ruptures. Coarctation stenting was performed in 8 animals. The coarctation was dilated from 5.8 +/- 0.9 mm to 9.8 +/- 0.6 mm (P < 0.001), and to 13.5 +/- 0.5 mm at redilation (P = 0.002). Redilation could not be performed in 1 animal. Aortic rupture and death occurred in 2 of 7 animals at redilation. Stent implantation and redilation in experimental pulmonary artery stenosis appears safe and effective. Though stent implantation for coarctation of the aorta appears safe, there was a 28% aortic rupture rate at stent redilation in this model.

Angioplasty, Balloon↗
PubMed1995

The effects of cyanosis on myocardial blood flow, oxygen utilization, and lactate production in dogs.

To elucidate differences in myocardial blood flow and metabolism between cyanotic and normal hearts, a model of chronic cyanosis was created in five adult mongrel dogs by anastomosing the inferior vena cava to the left atrium. After 6 to 9 months, myocardial blood flow, the ratio of subendocardial to subepicardial flow, oxygen consumption, oxygen extraction ratio, and lactate consumption in these cyanotic dogs and five control dogs were determined under baseline conditions and during pharmacologic stress with isoproterenol (0.2 micrograms/kg/min). Radioactive microspheres were used to determine left and right ventricular blood flow rates, and arterial and coronary sinus differences in oxygen and lactate levels were measured. At baseline and during stress, oxygen consumption and oxygen extraction ratios were identical in control and cyanotic hearts. Total myocardial blood flow was increased with stress and did not differ between cyanotic and control hearts. Left ventricular muscle from cyanotic hearts did exhibit lower endocardial/epicardial blood flow ratios than those of control hearts at rest, and the relative subendocardial flow decreased further with stress. During isoproterenol infusion, myocardial lactate production, indicative of anaerobic metabolism, was evident in two of five cyanotic animals and none of the control dogs. The relative subendocardial ischemia and its further aggravation by stress in cyanotic hearts may contribute to the pathophysiologic basis of myocardial dysfunction in cyanotic heart disease.

Animals↗
PubMed1994

Comparison of a low osmolarity nonionic radiographic contrast agent with a standard medium on renal function in cyanotic and normal dogs.

Renal dysfunction may follow administration of iodinated radiographic contrast agents. This complication may be less common when low osmolarity nonionic agents are used. Although potential benefits from the use of low osmolarity nonionic contrast may be minimal in individuals with normal physiology, a greater benefit has been postulated in the presence of chronic cyanosis. To test this hypothesis, six adult mongrel dogs underwent anastomosis of the inferior vena cava to the left atrium. This produced chronic cyanosis with a mean pO2 of 48 +/- 4 mm Hg and polycythemia with a mean hematocrit of 56 +/- 2 gm%. Three to 5 months after preparation, these cyanotic dogs and five control dogs each received diatrizoate (a high osmolarity ionic agent) or ioversol (a low osmolarity nonionic agent), 465 mg iodine/kg body weight, by intravenous bolus injection. One month later, each animal received the other agent. The order of administration was randomized. Renal function studies, including serum creatinine and creatinine clearance, were performed precontrast, after 60 min, and 24 hr postcontrast. Neither agent adversely affected renal function in either the cyanotic or the normal group. We conclude that at the doses that are commonly used in clinical practice, high osmolarity ionic contrast agents do not create a greater risk of renal injury than do low osmolarity nonionic agents in this model of cyanosis.

Angiocardiography↗
PubMed1994

Selective lung or heart-lung transplantation for pulmonary hypertension associated with congenital cardiac anomalies.

Fixed pulmonary hypertension has been a contraindication to correction of congenital heart defects. Beginning in February 1991, we pursued a policy of performing single-lung transplantation with intracardiac repair for selected patients with this physiology, reserving heart-lung transplantation for those with unreconstructable heart disease. Of 7 patients treated under this protocol, 5 underwent single-lung transplantation and intracardiac repair. The cardiac anomalies included complete atrioventricular canal (1), aortopulmonary window (1), atrial septal defect (1), and ventricular septal defect (2). One patient died perioperatively. All 4 patients surviving operation remained alive through the first postoperative year, but 3 died 13, 17, and 22 months after operation. Two other patients with pulmonary hypertension (1 with tricuspid atresia, 1 after failed Mustard procedure) received a heart-lung transplant and are well 15 and 18 months after operation. This experience demonstrates that selected patients with major intracardiac defects and pulmonary hypertension may have good early results after cardiac repair and single-lung transplantation, but that long-term results are considerably less favorable.

Adolescent↗
PubMed1994

Regulation of pulmonary vascular resistance by endogenous and exogenous nitric oxide.

Inhaled nitric oxide (NO) causes selective pulmonary vasodilation under conditions of hypoxia or pulmonary vascular dysfunction. We have observed that NO affects canine pulmonary vascular resistance minimally under normal conditions. We hypothesized that endogenous NO is partly responsible for pulmonary vasomotor regulation in normoxic and hypoxic states. Dogs were studied before and after pulmonary endothelial injury with monocrotaline and N-omega-nitro-L-arginine (LNNA). Systemic vascular resistance was unaffected by NO. Under normal conditions, exogenous NO had little effect on pulmonary vascular resistance. After monocrotaline administration, baseline pulmonary vascular resistance was unchanged but decreased further in response to NO. After LNNA administration, pulmonary vascular resistance increased and there was an exaggerated increase with hypoxia that was reduced by NO. The effect of monocrotaline on in vitro endothelial function was evaluated with isolated pulmonary arteries, which showed a decreased relaxation response to bradykinin (an endothelial-dependent vasodilator) and a normal response to nitroprusside (an endothelial-independent vasodilator). These results support the hypothesis that endogenous NO is an important regulator of pulmonary vasomotor tone and is of even greater importance during hypoxia.

Animals↗
PubMed1994

Systemic ventricular outflow obstruction progresses after the Fontan operation.

To evaluate the course of systemic ventricular outflow obstruction after the Fontan operation, the records of 57 hospital survivors of that procedure were reviewed. Ventricular outflow obstruction was identified in 7 patients (group 1) and was absent in 50 patients (group 2). Overall, the ventricular outflow gradient in group 1 was 6.3 +/- 2.9 mm Hg (mean +/- standard error) before the Fontan operation and 7.6 +/- 3.9 mm Hg at hospital discharge. Ventricular outflow obstruction subsequently progressed to 80.1 +/- 17.3 mm Hg (range, 33 to 165 mm Hg; p < 0.02) a mean of 28 months postoperatively. One patient died of severe progressive ventricular outflow obstruction. Group 1 did not differ from group 2 in age, ventricular morphology, presence of a subaortic outflow chamber, prior shunt, or length of follow-up. Compared with group 2, however, patients in group 1 more commonly had an aorta arising from a hypoplastic ventricle (p < 0.001) and had undergone prior pulmonary artery banding (p = 0.005). We conclude that systemic ventricular outflow obstruction occurs commonly after a Fontan procedure (incidence, 12%; 70% confidence interval, 9% to 18%) and is a progressive lesion.

Child, Preschool↗
PubMed1994

Improving results with first-stage palliation for hypoplastic left heart syndrome.

Between January 1990 and February 1993, 73 patients underwent first-stage reconstruction for hypoplastic left heart syndrome at the University of Michigan Medical Center. During this period, surgical reconstruction remained essentially constant and consisted of a pulmonary artery-to-aorta anastomosis with allograft augmentation of the ascending, transverse, and proximal descending aorta, restriction of pulmonary blood flow with a polytetrafluoroethylene shunt from the innominate artery to the central pulmonary artery confluence, and atrial septectomy. Hospital survival was 62 of 73 patients, 85% (70% confidence limits: 80% to 89%). These results stand in marked contrast to those obtained during the earlier years of our experience from 1986 to 1989 when only 21 of 50 patients (42%, 70% confidence limits: 35% to 49%) survived (p = 0.001). Among the most recent group of patients, only 2 of 7 patients older than 1 month of age at operation survived, whereas 60 of 66 (91%, 70% confidence limits: 87% to 94%) patients younger than 1 month of age survived (p = 0.0001). Anatomic subtype and ascending aortic diameter were not predictive of survival. Actuarial survivals for those patients younger than 1 month of age at the first-stage operation, including hospital deaths and subsequent operative procedures, were 81%, 74%, and 74% at 6 months, 1 year, and 2 years, respectively. These results indicate that survival for patients after first-stage reconstruction for hypoplastic left heart syndrome has significantly improved in recent years. Older age was a strong risk factor, with a hospital survival of 91% for those patients undergoing first-stage palliation within the first month of life. These data have important implications for the type of operative intervention and its timing.

Actuarial Analysis↗
PubMed1994

Effects of preservation techniques on in vivo expression of adhesion molecules by aortic valve allografts.

Methods of sterilization and preservation of aortic valve allografts influence graft longevity. The effect of storage techniques on valve durability may be mediated by alterations in the immunologic properties of the allograft, which are reflected by expression of leukocyte adhesion molecules. Rat aortic valve grafts were transplanted in the fresh state, after cryopreservation (-196 degrees C), or after storage at 4 degrees C for 1 to 21 days. Syngeneic and strongly allogeneic valves were transplanted for 4 hours to 21 days and were retrieved for immunohistochemical staining for expression of leukocyte adhesion molecules. Unimplanted valves and transplanted syngeneic valves, regardless of storage methods, exhibited little or no expression of leukocyte adhesion molecules. Fresh allogeneic valves expressed all molecules, indicating up-regulation, at all time intervals studied. Cryopreserved allogeneic valves demonstrated no leukocyte adhesion molecules at 4 hours or 2 days and weak reactivity at 10 and 21 days. Allogeneic valves stored at 4 degrees C, regardless of the duration of storage, demonstrated weak expression of all molecules at 10 days and strong expression at 21 days. Expression of leukocyte adhesion molecules requires an allogeneic environment and may precede immune-mediated injury. Reduced expression of leukocyte adhesion molecules resulting from storage may predict a diminished immunologic response. Cryopreservation (-196 degrees C) causes the greatest delay and diminution of expression of leukocyte adhesion molecules.

Animals↗
PubMed1994

Central pulmonary artery growth patterns after the bidirectional Glenn procedure.

The changes in pulmonary artery size and hemodynamics in 30 patients with univentricular cardiac anatomy were examined before and after bidirectional Glenn procedures done between October 1989 and February 1992. Serial angiographic and hemodynamic examinations before and 17.6 +/- 1.6 months after bidirectional Glenn procedures were compared. At the follow-up study there was no significant change in diameter of the pulmonary artery ipsilateral to the bidirectional Glenn shunt, however, a significant decrease was noted in the diameter of the pulmonary artery contralateral to the bidirectional Glenn shunt (p = 0.04). There was also a 32% decrease in the Nakata index of total cross-sectional pulmonary artery area after the bidirectional Glenn procedure (p = 0.004). Total pulmonary blood flow and mean pulmonary artery pressure had decreased, and arterial oxygen saturation had increased at follow-up. These changes, however, did not correlate with the observed changes in pulmonary artery size. By linear regression analysis, a significant relationship was identified between the Nakata index before the bidirectional Glenn procedure and the absolute change in Nakata index (r = 0.83). A significant decrease in Nakata index occurred only in patients with a bidirectional Glenn shunt in place more than 15 months. Sixteen of the 30 patients subsequently underwent total cavo-pulmonary anastomosis with 7 requiring concurrent surgical pulmonary artery reconstruction. Changes in pulmonary artery size observed more than 15 months after the bidirectional Glenn procedure may have implications for subsequent Fontan repair in children with univentricular anatomy.

Arteriovenous Shunt, Surgical↗