Pharmacologic pre-conditioning and controlled reperfusion prevent ischemia-reperfusion injury after 30 minutes of hypoxia/ischemia in porcine hearts.

BACKGROUND: Hearts from non-heart-beating organ donors are not transplanted because of risk of ischemia-reperfusion injury. We tested whether pharmacologic pre-conditioning with adenosine and the Na(+)/H(+) exchanger inhibitor, cariporide, combined with controlled reperfusion, would prevent injury in porcine hearts that had sustained 30 minutes of hypoxia/ischemia in closed-chest animals. METHODS: Hearts from Yorkshire pigs (100 kg) were studied in 3 groups. Group 1 (control) hearts were surgically removed while beating. Group 2 hearts were harvested from animals made hypoxic by discontinuing mechanical ventilation for 30 minutes. Group 3 hearts were hypoxic as in Group 2, but these animals received adenosine (40 mg) and cariporide (400 mg) 10 minutes before stopping ventilation. Cardiac function in all groups was assessed ex vivo in a working heart apparatus in which pressure and flow measurements were made over 3 hours. Controlled reperfusion in Group 3 hearts used leukocyte-depleted blood perfusate containing free radical scavengers. Myocardial injury was assessed on the basis of perfusate creatine phosphokinase activity and histopathologically determined injury score. RESULTS: Groups 1 and 3 hearts could be resuscitated to perform work equivalently during the entire reperfusion period and showed positive responses to increases in pre-load and norepinephrine. Group 2 hearts could not perform work. After 3 hours, Group 2 hearts showed significantly higher creatine phosphokinase and histopathologic injury scores compared to with Groups 1 and 3, which were not significantly different from each other. CONCLUSIONS: Pharmacologic pre-conditioning and controlled reperfusion effectively protect non-beating porcine hearts from injury after 30 minutes of hypoxia/ischemia in situ.

Electrophysiological alterations after mechanical circulatory support in patients with advanced cardiac failure.

BACKGROUND: Recognizing that mechanical circulatory support with a left ventricular assist device (LVAD) induces changes in myocardial structure and contractile function, we examined whether there are changes in ventricular conduction and/or repolarization among failing human hearts after LVAD implantation. METHODS AND RESULTS: We examined 12-lead electrocardiograms before surgery, immediately after LVAD placement, and at a delayed (>1 week) postoperative time point in 23 patients who were receiving LVAD support for refractory heart failure. The immediate effects of hemodynamic unloading via LVAD placement included a decrease in QRS duration from 117+/-6 to 103+/-6 ms (P<0.01), an increase in absolute QT duration from 359+/-6 to 378+/-8 ms (P<0.05), and an increase in the heart rate-corrected QT interval (QTc) from 379+/-10 to 504+/-11 ms (P<0.01). None of these immediate changes were observed among 22 patients undergoing routine coronary artery bypass grafting. With sustained cardiac unloading via LVAD support, there was a marked decrease in the QTc from 504+/-11 to 445+/-9 ms (P<0.001). Studies in isolated cardiac myocytes, obtained at the time of transplantation, confirmed that delayed decreases in heart rate-adjusted QTc were the result of decreases in action potential duration after LVAD support. CONCLUSIONS: Acute electrocardiogram responses to LVAD placement demonstrate the dependence of QRS and QT duration on load in the failing human heart. Delayed decreases in QTc and action potential duration reflect reversal of electrophysiologic remodeling in the failing heart. Shortening of the action potential duration likely contributes to the improved cellular contractile performance observed after sustained LVAD support.

Patients with end-stage congestive heart failure treated with beta-adrenergic receptor antagonists have improved ventricular myocyte calcium regulatory protein abundance.

BACKGROUND: Alterations in Ca(2+)-handling proteins are thought to underlie the deranged Ca(2+) transients that contribute to deterioration of cardiac function in congestive heart failure (CHF). Clinical trials in CHF patients have shown that treatment with beta-adrenergic receptor antagonists (betaB) improves cardiac performance. The present study determined whether the abundance of Ca(2+)-handling proteins is different in failing hearts from patients treated or untreated with beta B. METHODS AND RESULTS: Ca(2+) regulatory protein abundance was compared in LV myocardium of 10 nonfailing hearts (NF group) and 44 failing hearts (CHF group) removed at transplantation. Analysis was performed in betaB-treated (betaB-CHF) and non-betaB treated (non-betaB-CHF) patients and in 4 subgroups: ischemic cardiomyopathy (ICM, n=10), nonischemic dilated cardiomyopathy (DCM, n=10), ICM with betaB therapy (betaB-ICM, n=12), and DCM with betaB therapy (betaB-DCM, n=12). Sarcoplasmic reticulum Ca(2+) ATPase, phospholamban, and Na(+)-Ca(2+) exchanger protein abundance were determined by use of Western blot analysis. Ca(2+) transients were measured with fluo-3. Sarcoplasmic reticulum Ca(2+) ATPase was significantly less abundant whereas phospholamban and Na(+)-Ca(2+) exchanger were not significantly altered in non-betaB-CHF versus NF. Sarcoplasmic reticulum Ca(2+) ATPase in the betaB-ICM and betaB-DCM was greater than in non-betaB-CHF and were not different than in NF. Ca(2+) transients in non-betaB-CHF myocytes had significantly smaller peaks and were prolonged versus NF myocytes. Ca(2+) transients from betaB-CHF myocytes had shorter durations than in betaB-CHF myocytes. CONCLUSIONS: betaB treatment in CHF patients can normalize the abundance of myocyte Ca(2+) regulatory proteins and improve Ca(2+)-handling.

Abnormalities of calcium cycling in the hypertrophied and failing heart.

Progressive deterioration of cardiac contractility is a central feature of congestive heart failure (CHF) in humans. In this report we review those studies that have addressed the idea that alterations of intracellular calcium (Ca(2+)) regulation is primarily responsible for the depressed contractility of the failing heart. The review points out that Ca(2+)transients and contraction are similar in non-failing and failing myocytes at very slow frequencies of stimulation (and other low stress environments). Faster pacing rates, high Ca(2+)and beta-adrenergic stimulation reveal large reductions in contractile reserve in failing myocytes. The underlying cellular basis of these defects is then considered. Studies showing changes in the abundance of L-type Ca(2+)channels, Ca(2+)transport proteins [sarcoplasmic reticulum Ca(2+)ATPase (SERCA2), phospholamban (PLB), Na(+)/Ca(2+) exchanger (NCX)] and Ca(2+) release channels (RYR) in excitation-contraction coupling and Ca(2+)release and uptake by the sarcoplasmic reticulum (SR) are reviewed. These observations support our hypotheses that (i) defective Ca(2+)regulation involves multiple molecules and processes, not one molecule, (ii) the initiation and progression of CHF inolves defective Ca(2+)regulation, and (iii) prevention or correction of Ca(2+)regulatory defects in the early stages of cardiac diseases can delay or prevent the onset of CHF.

Voltage-dependent Ca2+ release from the SR of feline ventricular myocytes is explained by Ca2+-induced Ca2+ release.

1. Direct voltage-gated (voltage-dependent Ca2+ release, VDCR) and Ca2+ influx-gated (Ca2+-induced Ca2+ release, CICR) sarcoplasmic reticulum (SR) Ca2+ release were studied in feline ventricular myocytes. The voltage-contraction relationship predicted by the VDCR hypothesis is sigmoidal with large contractions at potentials near the Ca2+ equilibrium potential (ECa). The relationship predicted by the CICR hypothesis is bell-shaped with no contraction at ECa. 2. The voltage dependence of contraction was measured in ventricular myocytes at physiological temperature (37 C), resting membrane potential and physiological [K+]. Experiments were performed with cyclic adenosine 3',5'-monophosphate (cAMP) in the pipette or in the presence of the beta-adrenergic agonist isoproterenol (isoprenaline; ISO). 3. The voltage-contraction relationship was bell-shaped in Na+-free solutions (to eliminate the Na+ current and Na+-Ca2+ exchange, NCX) but the relationship was broader than the L-type Ca2+ current (ICa,L)-voltage relationship. 4. Contractions induced with voltage steps from normal resting potentials to -40 mV are thought to represent VDCR rather than CICR. We found that cAMP and ISO shifted the voltage dependence of ICa,L activation to more negative potentials so that ICa,L was always present with steps to -40 mV. ICa,L at -40 mV inactivated when the holding potential was decreased (VL = -57.8 +/- 0.49 mV). 5. ISO increased inward current, SR Ca2+ load and contraction in physiological [Na+] and a broad bell-shaped voltage-contraction relationship was observed. Inhibition of reverse-mode NCX, decreasing ICa,L and decreasing SR Ca2+ loading all decreased contractions at strongly positive potentials near ECa. 6. The voltage-contraction relationship in 200 microM cadmium (Cd2+) was bell-shaped, supporting a role of ICa,L rather than VDCR. 7. All results could be accounted for by the CICR hypothesis, and many results exclude the VDCR hypothesis.

Cost analysis of an Italian ICU.

BACKGROUND: Cost reduction is an important issue in medicine today, especially when considering ICUs, since they account for a large percentage of all hospital expenditure. Through a retrospective analysis of the data regarding the expenses incurred during the years 1996-97, we have been able to evaluate the total costs of our ICU and the influence that each component had on the final costs, thus gathering the necessary information for the improvement of the unit itself. METHODS: Retrospective analysis of a 5-bedded multidisciplinary ICU activity over a two-year period (1996-1997). Cost-related data have been supplied by the Hospital Administration as to wages, infrastructures, equipment buying and maintenance; by Hospital Pharmacy as to drugs and devices supplies; and by Laboratory and Radiology as to diagnostic investigations. RESULTS: According to our experience, physicians and non-medical staff account for more than 50% of the total expenditure--the latter slightly prevailing. Furthermore, we have assessed that the cost distribution is hardly comparable to that reported by other authors. CONCLUSIONS: It is useful to analyse the total distribution and to evaluate their nature only to gain the necessary data that will lead to a more effective management of the unit. Nevertheless, this methodology is valid within the cost analysis of our ICUs but the ICUs of other countries show great differences in the way they are structured and some of the use more reliable activity-based costing methodology.

Functional properties of failing human ventricular myocytes.

Reduced peak systolic Ca2+ and slow decay of the Ca2+ transient are common features of the end-stage failing human ventricular myocyte and are thought to underlie abnormal ventricular contractility in congestive heart failure (CHF). Individual changes in the expression or activity of Ca2+ transport proteins of the sarcoplasmic reticulum (SR Ca2+ ATPase, SERCa) or the sarcolemmal (sodium-calcium exchanger, NCX) have not always been observed in CHF and cannot per se consistently explain these Ca2+ transient defects. We review recent data that suggests that the normal balance of transport activities of SERCa and NCX is deranged in failing human myocytes. We hypothesize that an increase in the NCX/SERCa transport capacity in failing myocytes can explain the abnormal Ca2+ homeostasis of the failing human ventricular myocyte.

[Pulmonary re-expansion edema. Description of two cases and observations about its management]. / L'edema polmonare da riespansione. Descrizione di due casi e considerazioni sulla sua gestione.

Two cases of Reexpansion pulmonary edema (RPE), an uncommon complication of the treatment of chronic lung collapse secondary to pneumothorax or pleural effusion, are described. RPE is generally unilateral and occurs when the lung is rapidly reexpanded by active evacuation of large amounts of air or fluid. Nevertheless, both cases observed confirm that RPE can be seen when the pulmonary collapse is of short duration and the lung is reexpanded without suction. The pathogenesis of RPE is still unclear and is probably multifactorial. Implicated in the etiological process of RPE are chronicity of collapse, technique of reexpansion, increased pulmonary vascular permeability, airway obstruction, loss of surfactant, and pulmonary artery pressure changes. In the observed cases RPE appeared unexpectedly and dramatically, which is typical of the condition. The edema progressed for 24-48 hours, although it may persist for 4-5 days. Therapy was supportive and proportional to the severity of the clinical picture. Both needed mechanical ventilation, while only in case 1 was a hemodynamic support applied. Since the outcome is still fatal in 20% of cases, physicians treating chronic lung collapse must be aware of the possible causes and try to prevent the occurrence of this complication.

Sodium/calcium exchange contributes to contraction and relaxation in failed human ventricular myocytes.

Defects in myocyte contraction and relaxation are key features of human heart failure. Sodium/calcium exchanger-mediated contribution to contraction and relaxation were separated from other mechanisms [L-type calcium current, sarco(endo)plasmic reticulum (SR) Ca(2+)-ATPase] based on voltage, temperature, and selective blockers. Rod-shaped left ventricular myocytes were isolated from failed human explants (n = 29) via perfusion with collagenase-containing Krebs solution. Action potentials using perforated patch and contractions using an edge detector were recorded at 0.5-1.5 Hz in Tyrode solution at 25 degrees C and 37 degrees C. Contraction duration was dependent on action potential (AP) duration at 37 degrees C but not at 25 degrees C, suggesting the role of the exchanger in relaxation and linking myocyte relaxation to the repolarization phase of the AP. Voltage-clamp experiments from -50 to +10 mV for 1,500 ms in Tyrode or Na(+)- and K(+)-free solutions after conditioning pulses triggered biphasic contractions that included a rapid SR-mediated component and a slower voltage-dependent exchanger-mediated component. We used thapsigargin to block the SR, which eliminated the rapid component, and we used an exchanger blocker, Kanebo 7943, which eliminated the slow component. The exchanger was shown to contribute to contraction through reverse-mode exchange, as well as to play a key role in relaxation of human ventricular myocytes.

[The effect of anesthesiologic technique on the mental state of elderly patients submitted for orthopedic surgery of the lower limbs]. / Influenza della condotta anestesiologica sullo stato mentale di soggetti anziani sottoposti a chirurgia ortopedica dell'arto inferiore.

UNLABELLED: Influence of anesthetic technique on mental status in elderly patients submitted to major orthopedic procedures of lower limbs. Mental impairment is a common occurrence in elderly patients after major orthopedic surgery. Few studies have been published so far on this topic in spite of its relevant clinical and economic implications. OBJECTIVE: 1) To verify whether anesthesia has a causative role in postoperative mental confusion in elderly patients; 2) to compare the effects of General Anesthesia (GA) and Spinal Anesthesia (SA) on mental status. DESIGN: Controlled, comparative study. PATIENTS: Sixty patients aged > or = 70, ASA I-II, submitted to femoral neck repair. SETTING: Anesthesia Dept. and Orthopedic Dept. of a District Hospital in Italy. METHOD: The day before surgery the mental status of elected patients was evaluated employing a modified Organic Brain Syndrome (OBS) scale (Gustafsson). The better the mental status, the lesser the OBS score. It was possible therefore to distinguish "oriented" from "confuse" patients (38 vs 22) if they scored < or = 6 or > 6 respectively. Patients from each group were than randomly assigned to receive either GA or selective SA. Neither group was premedicated. GA was induced with propofol 1 mg/kg and maintained with O2/N2O 40/60% and isoflurane; atracurium was employed to facilitate mioresolution. Spinal anesthesia was performed with hyperbaric 1% bupivacaine. All patients were monitored in the Recovery Room (RR) for at least one hour. Occurrence of hypotension and/or hypoxia in the Operating Room (OR) or the RR was immediately treated. Mental status was reassessed on the 1st and 2nd postoperative day and results were compared with the corresponding preoperative OBS scores both in GA patients and in SA patients. RESULTS: No statistically significant differences were found between pre- and postoperative OBS scores in both GA and SA group, whether "oriented" or "confuse". CONCLUSIONS: Mental status of elderly patients submitted to femoral neck repair doesn't seem to be influenced by the anesthetic technique chosen, independent of preoperative psychic conditions.

[An epidemiological study of cardiac emergency cases in the province of Florence and the Southeast Florence Hospital area]. / Indagine epidemiologica sulle emergenze cardiologiche nella provincia di Firenze e nel comprensorio ospedaliero Firenze sud-est.

The national data provided by ANMCO in 1978 show a total of 2.5 m heart cases in Italy, including 1.5 m instances of ischaemic cardiopathy, and an annual incidence of 105,000 new cases of myocardial infarct. An assessment was made of the 1976 and 1977 pattern of "cardiological emergency cases" (ISTAT codes 402, 410-14, 427-29, 441, 450, 519, 997) in the province of Florence and two of its social and health consortia: 39 (municipalities of Dicomano, Londa, Pelago, Pontassieve, Rufina, S. Godenzo), and 51 (municipalities of Borgata Ripoli, Greve, Impruneta, S. Casciano, Tavarnelle). The records of the S. Maria Nuova, Florence Hospital were used for in-patient data, since this is the only hospital in the province with automatic filing by discharge diagnosis according to the ISTAT code. Mortality in emergency cases in the two consortia m and the province fell from 14.68% and 17.17% to 11.20% and 18.11% respectively in the two years. In both populations, the highest incidence was between 70 and 74 yr of age in 1976, and between 65 and 69 yr in 1977. In the case of infarct, mortality moved from 18.75 to 7.58% (consortia) and from 22.40% to 20.93% (province), with maximum incidences in 1976 between 70 and 74 yr (consortia and province), and in 1977 between 65 and 69 yr (province) and between 55 and 59 yr (consortia). Admissions were greatest in number on Mondays (peak hours: 11 a.m. to 4 p.m.) whereas no difference was noted between one month and another. The Hospital Resuscitation Centre, which serves the two consortia, received 45 emergency cases in 1977, including 25 infarct patients. Total mortality was 13.33% (infarct 20%). The slight numeric discrepancy between in the latter data and those held in the computer suggests that the ISTAT code may not be easy to use and not always employed by physicians in a rational manner.