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Biomedical subjects

D Morabito

Publications and source records attributed to D Morabito.

At least 19 recordsLinked to original sources
PubMed2002

Impaired glucose metabolism in the heart of obese Zucker rats after treatment with phorbol ester.

OBJECTIVE: To investigate the influence of obesity on the regulation of myocardial glucose metabolism following protein kinase C (PKC) activation in obese (fa/fa) and lean (Fa/?) Zucker rats. DESIGN: Isolated hearts obtained from 17-week-old lean and obese Zucker rats were perfused with 200 nM phorbol 12-myristate 13-acetate (PMA) for different time periods prior to the evaluation of PKC and GLUT-4 translocation. For metabolic studies isolated hearts from 48 h starved Zucker rats were perfused with an erythrocytes-enriched buffer containing increased concentrations (10-100 nM) of PMA. MEASUREMENTS: Immunodetectable PKC isozymes and GLUT-4 were determined by Western blots. Glucose oxidation and glycolysis were evaluated by measuring the myocardial release of 14CO2 and 3H2O from [U-14C]glucose and [5-3H]glucose, respectively. RESULTS: PMA (200 nM) induced maximal translocation of ventricular PKCalpha from the cytosol to the membranes within 10 min. This translocation was 2-fold lower in the heart from obese rats when compared to lean rats. PMA also induced a significant translocation of ventricular GLUT-4 from the microsomal to the sarcolemmal fraction within 60 min in lean but not in obese rats. Rates of basal cardiac glucose oxidation and glycolysis in obese rats were approximately 2-fold lower than those of lean rats. Perfusion with increasing concentrations of PMA (10-100 nM) led to a significant decrease of cardiac glucose oxidation in lean but not in obese rats. CONCLUSION: Our results show that in the heart of the genetically obese Zucker rat, the impairment in PKCalpha activation is in line with a diminished activation of GLUT-4 as well as with the lack of PMA effect on glucose oxidation.

Animals↗
PubMed2001

Hypotension, hypoxia, and head injury: frequency, duration, and consequences.

BACKGROUND: Retrospective studies have suggested an association between systemic hypotension and hypoxia and worsened outcome from traumatic brain injury. Little is known, however, about the frequency and duration of these potentially preventable causes of secondary brain injury. HYPOTHESIS: Early episodes of hypoxia and hypotension occurring during initial resuscitation will have a significant impact on outcome following traumatic brain injury. DESIGN: Prospective cohort study. SETTING: Urban level I trauma center. PATIENTS: Patients with a traumatic brain injury who had a Glasgow Coma Score of 12 or less within the first 24 hours of admission to the hospital and computed tomographic scan results demonstrating intracranial pathologic features. Patients who died in the emergency department were excluded from the study. MAIN OUTCOME MEASURES: Automated blood pressure and pulse oximetry readings were collected prospectively from the time of arrival through initial resuscitation. The number and duration of hypotensive (systolic blood pressure, < or =90 mm Hg) and hypoxic (oxygen saturation, < or =92%) events were analyzed for their association with mortality and neurological outcome. RESULTS: One hundred seven patients met the enrollment criteria (median Glasgow Coma Score, 7). Overall mortality was 43%. Twenty-six patients (24%) had hypotension while in the emergency department, with an average of 1.5 episodes per patient (mean duration, 9.1 minutes). Of these 26 patients with hypotension, 17 (65%) died (P =.01). When the number of hypotensive episodes increased from 1 to 2 or more, the odds ratio for death increased from 2.1 to 8.1. Forty-one patients (38%) had hypoxia, with an average of 2.1 episodes per patient (mean duration, 8.7 minutes). Of these 41 patients with hypoxia, 18 (44%) died (P =.68). CONCLUSIONS: Hypotension, but not hypoxia, occurring in the initial phase of resuscitation is significantly (P =.009) associated with increased mortality following brain injury, even when episodes are relatively short. These prospective data reinforce the need for early continuous monitoring and improved treatment of hypotension in brain-injured patients.

Adolescent↗
PubMed2001

Carbon dioxide reactivity and pressure autoregulation of brain tissue oxygen.

OBJECTIVE: To describe the normal relationships between brain tissue oxygen tension (PbrO2) and physiological parameters of systemic blood pressure and CO2 concentrations. METHODS: Licox Clark-type oxygen probes (GMS mbH, Kiel, Germany) were inserted in the frontal white matter of 12 swine maintained under general anesthesia with a 1.0 fraction of inspired oxygen (FiO2). In seven swine, alterations in end-tidal carbon dioxide (ET-CO2) concentration (range, 13-72 mm Hg) were induced via hyperventilation or instillation of CO2 into the ventilation circuit. In nine swine, mean arterial pressure (MAP) (range, 33-200 mm Hg) was altered; phenylephrine was used to induce hypertension, and a nitroprusside-esmolol combination or systemic hemorrhage was used for hypotension. Quantitative cerebral blood flow (CBF) was measured in two animals by using a thermal diffusion probe. RESULTS: Mean baseline PbrO2 was 41.9 +/- 11.3 mm Hg. PbrO2 varied linearly with changes in ET-CO2, ranging from 20 to 60 mm Hg (r2 = 0.70). The minimum PbrO2 with hypocarbia was 5.9 mm Hg, and the maximum PbrO2 with hypercarbia was 132.4 mm Hg. PbrO2 varied with MAP in a sigmoid fashion suggestive of pressure autoregulation between 60 and 150 mm Hg (r2 = 0.72). The minimum PbrO2 with hypotension was 1.4 mm Hg, and the maximum PbrO2 with hypertension was 97.2 mm Hg. In addition, CBF correlated linearly with PbrO2 during CO2 reactivity testing (r2 = 0.84). CONCLUSION: In the uninjured brain, PbrO2 exhibits CO2 reactivity and pressure autoregulation. The relationship of PbrO2 with ET-CO2 and MAP appears to be similar to those historically established for CBF with ET-CO2 and MAP. This suggests that, under normal conditions, PbrO2 is strongly influenced by factors that regulate CBF.

Animals↗
PubMed2001

Obesity is associated with impaired ventricular protein kinase C-MAP kinase signaling and altered ANP mRNA expression in the heart of adult Zucker rats.

BACKGROUND: In the obesity model of the Zucker rat, myocardial protein kinase C (PKC) activation by phorbol ester is impaired. The influence of obesity on myocardial cell signaling was investigated by studying the activation of PKC isozymes and MAP kinases (MAPK) p38 and p42/44 as well as the induction of ANP mRNA. METHODS: Isolated hearts obtained from 17-week-old lean and obese Zucker rats were perfused with 200 nM phorbol 12-myristate 13-acetate (PMA) at different time periods. Immunodetectable PKC isozymes, phosphorylated-MAPK, and ANP mRNA were determined by Western and Northern blots, respectively. RESULTS: PMA promoted a marked transient translocation of ventricular PKCalpha from the cytosol to the membranes within 10 minutes in lean rats, whereas it had a much weaker effect in obese rats. Moreover, PMA induced a significant activation of PKCdelta in lean but not in obese rat hearts. After PKC activation, increases in phosphorylation levels of myocardial p38 and p42 MAPK were approximately 3-fold higher in lean rats than in obese animals. Concerning the induction of ANP, PMA transiently tripled ANP mRNA within 60 minutes in lean but not in obese rats. CONCLUSIONS: In the genetically obese Zucker rat, the myocardial signal transduction cascade PKC-MAPK-ANP mRNA seems to be markedly impaired. It can be speculated that this abnormal cardiac cell signaling in obese rats reflects an early phase in the cardiac pathogenesis accompanying obesity.

Animals↗
PubMed2000

Cerebral oxygenation during hemorrhagic shock: perils of hyperventilation and the therapeutic potential of hypoventilation.

OBJECTIVES: Prophylactic hyperventilation of patients with head injuries worsens outcome, presumably by exacerbating tissue hypoxia. Oxygen tension in brain tissue (PbrO2) provides a direct measurement of cerebral metabolic substrate delivery and varies with changing end-tidal carbon dioxide tension (ETCO2) and mean arterial pressure. However, the effects of hyperventilation and hypoventilation on PbrO2 during hemorrhagic shock are not known. The aim of this study was to examine the effects of alteration in ventilation on PbrO2 in hemorrhaged swine. METHODS: Clark-type polarographic probes were inserted into the brain tissue of seven swine to measure PbrO2 directly. To examine the effects of alterations in ventilation on hemorrhage-induced hypotension, swine were hemorrhaged to 50% estimated blood volume and PbrO2 was monitored during hyperventilation (RR = 30) and hypoventilation (RR = 4). RESULTS: After the 50% hemorrhage, PbrO2 declined rapidly from 39.8 +/- 4.6 mm Hg to 11.4 +/- 2.2 mm Hg. Hyperventilation resulted in a further 56% mean decrease in PbrO2. Hypoventilation produced a 166% mean increase in PbrO2. These changes were significant (p = 0.001) for absolute and percentage differences from baseline. CONCLUSION: During hemorrhage, alterations in ventilation significantly changed PbrO2: hyperventilation increased brain-tissue hypoxia whereas hypoventilation alleviated it. This finding suggests that hyperventilation has deleterious effects on brain oxygenation in patients with hemorrhagic shock and those with head trauma. Conversely, hypoventilation with resultant hypercapnia may actually help resolve hemorrhagic shock-induced cerebral hypoxia.

Animals↗
PubMed2000

Role of cell contractions in cAMP-induced cardiomyocyte atrial natriuretic peptide release.

Incubation of spontaneously beating ventricular cardiomyocytes from neonatal rats with prostaglandin E(2) (0.1 microM) or forskolin (0.1 microM) simultaneously increased the rate of cellular contraction and atrial natriuretic peptide (ANP) secretion. Both responses were maximal within 10-20 min of application and were accompanied by three- to fourfold increases in cAMP formation. By contrast, a higher regimen of forskolin (10 microM) promoted a 20- to 30-fold increase in basal cAMP production, which was accompanied by the abolition of contractile activity and ANP release. Low regimens of forskolin (0.1 microM) doubled the occurrence of cytosolic Ca(2+) transients associated with monolayer contraction, whereas higher regimens of forskolin (10 microM) completely suppressed Ca(2+) transients. Moreover, in quiescent cultures that were pretreated with ryanodine, tetrodotoxin, nifedipine, or butanedione monoxime, prostaglandin E(2) (0.1 microM) and forskolin (0.1 microM) failed to elicit significant ANP secretion, suggesting that cAMP-elevating agents promote ANP secretion to a great extent via an increase in cellular contraction frequency in ventricular cardiomyocytes.

Animals↗
PubMed1999

Brain tissue oxygenation during hemorrhagic shock, resuscitation, and alterations in ventilation.

OBJECTIVES: Recently developed polarographic microelectrodes permit continuous, reliable monitoring of oxygen tension in brain tissue (PbrO2). The aim of this study was to investigate the feasibility and utility of directly monitoring PbrO2 in cerebral tissue during changes in oxygenation or ventilation and during hemorrhagic shock and resuscitation. We also sought to develop a model in which treatment protocols could be evaluated using PbrO2 as an end point. METHODS: Licox Clark-type polarographic probes were inserted in the brain tissue of 16 swine to monitor PbrO2. In eight swine, changes in PbrO2 were observed over a range of fractional concentrations of inspired O2 (FiO2) as well as during periods of hyperventilation and hypoventilation. In eight other swine, PbrO2 was monitored during a graded hemorrhage of up to 70% estimated blood volume and during the resuscitation period. RESULTS: When FiO2 was elevated to 100%, PbrO2 increased from a baseline of 15+/-2 mm Hg to 36+/-11 mm Hg. Hyperventilation while breathing 100% oxygen resulted in a 40% decrease in PbrO2 (p < 0.05), whereas hypoventilation increased PbrO2 to 88 mm Hg (p < 0.01). A graded hemorrhage to 50% estimated blood volume significantly reduced PbrO2, mean arterial pressure, and intracranial pressure (p < 0.01). Continued hemorrhage to 70% estimated blood volume resulted in a PbrO2 of 2.9+/-1.5 mm Hg. After resuscitation, PbrO2 was significantly elevated, reaching 65+/-13 mm Hg (p < 0.01), whereas mean arterial pressure and cerebral perfusion pressure simply returned to baseline. CONCLUSION: Directly measured PbrO2 was highly responsive to changes in FiO2, ventilatory rate, and blood volume in this experimental model. In particular, hypoventilation significantly increased PbrO2, whereas hyperventilation had the opposite effect. The postresuscitation increase in PbrO2 may reflect changes in both O2 delivery and O2 metabolism. These experiments set the stage for future investigations of a variety of resuscitation protocols in both normal and injured brain.

Animals↗
PubMed1998

Fasciotomy, chronic venous insufficiency, and the calf muscle pump.

OBJECTIVE: To test the hypothesis that fasciotomy may impair the function of the calf muscle pump, which in turn could result in the development of chronic venous insufficiency. DESIGN: A cohort study of patients with a history of lower extremity fasciotomy. SETTING: An urban trauma center. PATIENTS: Seventeen of the 83 patients identified through trauma, vascular, and/or orthopedic registries consented to participation in this study. INTERVENTIONS: Participating patients completed a study questionnaire, and then underwent a complete vascular examination, including air plethysmographic (APG) assessment. Patients with a history of venous injuries were also studied with color flow duplex venous imaging. MAIN OUTCOME MEASURES: Function of the calf muscle pump as measured by APG, and evidence of chronic venous insufficiency as measured by APG, findings on clinical examination, and by venous ultrasonography. RESULTS: Seventeen patients completed the study, including 8 with a history of vascular injuries, 6 with old fractures, and 3 who had undergone fasciotomy for soft tissue infections. The time from injury to examination ranged from 5 months to 20 years. Eight patients had signs or symptoms of venous insufficiency, the severity of which appeared to be time dependent. The APG data showed significant mean differences between fasciotomy and control extremities in ejection fraction (P<.001) and residual volume fraction (P<.001), both measures of calf muscle pump function. There were no significant changes in venous filling index, a measure of venous reflux, or in outflow fraction, which correlates with venous obstruction. There were no differences in APG variables between patients with vascular injuries vs those with orthopedic or soft tissue injuries. CONCLUSIONS: Lower extremity fasciotomy impairs long-term calf muscle pump function, as measured by APG, in patients with and without vascular injuries. These patients are at risk for the long-term development of chronic venous insufficiency following lower extremity trauma.

Adult↗
PubMed1997

Use of tissue oxygen tension measurements during resuscitation from hemorrhagic shock.

BACKGROUND: Tissue oxygen tension can be measured directly in selected organ beds, and these measurements may be more sensitive in assessing the adequacy of resuscitation than global physiologic parameters. We hypothesized that heart tissue oxygen tension would be an important marker for the severity of ischemic insult to the heart during hemorrhagic shock. We further hypothesized that gut oxygen tension measured in the jejunum would prove to be a better measure of splanchnic hypoperfusion than intramucosal pH (pHi). METHODS: Tissue oxygen probes were inserted directly into the myocardium of the left ventricle and into the lumen of the proximal jejunum in 10 anesthetized swine. A pHi catheter was introduced into the stomach. The animals were subjected to a controlled hemorrhage of 50% of estimated blood volume. Gut and cardiac oxygen were monitored continuously during hemorrhage and resuscitation, which was performed with shed blood and crystalloid. RESULTS: While gut O2 and pHi trended together, we were unable to establish a correlation between changes in these two variables during hemorrhage and resuscitation. Heart PO2 decreased significantly during hemorrhage, but surpassed baseline values after resuscitation, a finding not seen in gut PO2. No standard physiologic variables reliably predicted changes in heart PO2 during these experiments. CONCLUSIONS: Tissue oxygen tensions measurements are highly responsive to changes induced during graded hemorrhagic shock and resuscitation. Gut PO2 and pHi appear to be measuring different physiologic processes in the gastrointestinal tract. The compensatory ability of the heart far exceeds that of the gut after ischemic insult. This hemorrhagic shock model appears feasible for the study of various methods of resuscitation.

Animals↗
PubMed1997

Role of cAMP and calcium influx in endothelin-1-induced ANP release in rat cardiomyocytes.

The mechanism of endothelin-1 (ET-1)-induced atrial natriuretic peptide (ANP) release was studied in neonatal rat ventricular cardiomyocytes. These cells expressed a single high-affinity class of ETA receptor (dissociation constant = 54 +/- 18 pM, n = 3), but no ETB receptors. Incubation of cardiomyocytes with ET-1 led to concentration-dependent ANP release and prostacyclin production. ET-1-induced ANP release was affected by neither protein kinase C (PKC) inhibition or downregulation nor by cyclooxygenase inhibition, indicating that ET-1-stimulated ANP secretion is not a PKC-mediated, prostaglandin-dependent process. Furthermore, ET-1 significantly stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production and increased cytosolic calcium concentration in these preparations. Both ET-1-induced calcium influx and ANP release were decreased by the cAMP antagonist Rp-cAMPS, the Rp diastereoisomer of cAMP. Moreover, ET-1-induced ANP secretion was strongly inhibited in the presence of nifedipine as well as in the absence of extracellular calcium. Thus our results suggest that ET-1 stimulates ANP release in ventricular cardiomyocytes via an ETA receptor-mediated pathway involving cAMP formation and activation of a nifedipine-sensitive calcium channel.

Alkaloids↗
PubMed1996

Use of low molecular weight heparin in preventing thromboembolism in trauma patients.

OBJECTIVE: To investigate the safety and effectiveness of low molecular weight heparin (LMWH) in preventing deep venous thrombosis (DVT) in high-risk trauma patients, compared with mechanical methods of prophylaxis. DESIGN: A prospective randomized trial conducted over a 19-month period in an urban, academic trauma center. METHODS: All trauma patients with the following risk factors for the development of DVT were considered for enrollment in this study: any injury with an Abbreviated Injury Scale score > or = 3; major head injury (Glasgow Coma Scale score < or = 8); spine, pelvic, or lower extremity fractures; acute venous injury; or age > 50 years. After a screening venous duplex examination, the patients were assigned to a Heparin versus No-Heparin group, depending upon the presence of injuries precluding the use of heparin. In the Heparin group, the patients were then randomized to receive either LMWH or optimal mechanical compression (defined as bilateral sequential gradient pneumatic compression (SCD) or, in the presence of lower extremity injuries precluding the use of the SCD, the arteriovenous impulse (AVI) compression system). All the patients in the No-Heparin group received optimal compression. Enrolled patients underwent sequential duplex examinations every 5 to 7 days until discharge. RESULTS: Of the 487 consecutive patients initially enrolled in this study, 372 were available for at least the first two duplex examinations and comprise the study population. Only nine (2.4%) patients developed DVT, compared with the predicted 9.1% rate in high-risk trauma patients receiving no prophylaxis (p = 0.037). Of the 120 patients who were randomized to receive LMWH, only one (0.8%) developed DVT. In the SCD group, there were 5 of 199 patients (2.5%) with DVT, and 3 of 53 (5.7%) in the AVI group. One patient with DVT also had clinical symptoms of pulmonary embolism, but there were no deaths secondary to pulmonary embolism. There was one major bleeding complication potentially associated with the use of LMWH. CONCLUSIONS: The administration of LMWH is a safe and extremely effective method of preventing DVT in high-risk trauma patients. When heparin is contraindicated, aggressive attempts at mechanical compression are warranted.

Adult↗
PubMed1995

Risks, costs, and the expected complication of re-injury.

BACKGROUND: The purpose of this study was to determine the characteristics of young victims of violence and the risk of rehospitalization due to intentional injury (recidivism) and to estimate the potential cost of these injuries. MATERIALS AND METHODS: Trauma admissions from January 1, 1991 to December 31, 1993, at San Francisco General Hospital of youths < 25 years old who were victims of gunshot wounds (GSWs), assault, and stab wounds were screened. Five hundred and fifty-two charts were reviewed after sampling every other chart. The cost of hospitalization was estimated from the Medicare charge-to-cost ratio. RESULTS: There were 87 (16%) persons who had a prior injury, of whom 82 (94%) had suffered their injury within the previous 5 years. The predominate mechanism of injury was GSW (242, 44%). There were 38 deaths; 35 (92%) were by firearms. The estimated cost of hospitalization for 552 youths for 3 years was $3,843,545.58. CONCLUSIONS: Intentional injury is a major risk factor and potential predictor for re-injury. Firearms are a major mechanism of intentional injury among youths and a major determinate of death. With the estimated cost of $2,562,363.72 per year for all youths at our hospital, intentional injury is a major health care issue for youths and hospitals.

Adolescent↗
PubMed1995

Trauma centers in a managed care environment.

Health care reform will affect the relationship of trauma centers to health maintenance organizations and other managed care plans. We studied Kaiser Permanente Medical Center (Kaiser) members admitted to the Trauma Center at San Francisco General Hospital (SFGH) to determine: (1) variables predicting transfer from SFGH to a Kaiser Hospital (repatriation), (2) the length of hospital stay (LOS), and (3) the cost of their care. The SFGH trauma registry provided data on 7,794 patients admitted before 1994. To investigate LOS, 89 Kaiser patients over 1 year were matched with non-Kaiser patients on age, maximum Abbreviated Injury Scale score (MAIS) by body region, Injury Severity Score (ISS), head injury severity, and blunt or penetrating injury and disposition. Kaiser patients were significantly younger, more likely to have blunt injury, and had a lower death rate. Significant predictors of repatriation were an MAIS score > or = 3, abdominal or extremity injury, and an ISS score of 26 to 40. The mean LOS for all Kaiser patients was 7.6 days, compared with 4.8 for controls (p = 0.20). However, mean LOS was significantly longer in repatriated Kaiser patients compared with controls (16 vs. 7.8 days, p < 0.0005). Kaiser reimbursement rates were comparable with commercial payors, but higher than others. A relatively small number of severely injured patients account for a large percentage of costly trauma care. Analyses of patient subsets are necessary for trauma centers to negotiate suitable relationships with managed care plans. A prospective study is needed to examine the cost efficiency of early transfer of managed care patients.

Adult↗