Pathophysiology and pathogenesis of stunned myocardium. Depressed Ca2+ activation of contraction as a consequence of reperfusion-induced cellular calcium overload in ferret hearts.

Contractile dysfunction in stunned myocardium could result from a decrease in the intracellular free [Ca2+] transient during each beat, a decrease in maximal Ca2+-activated force, or a shift in myofilament Ca2+ sensitivity. We measured developed pressure (DP) at several [Ca]0 (0.5-7.5 mM) in isovolumic Langendorff-perfused ferret hearts at 37 degrees C after 15 min of global ischemia (stunned group, n = 13) or in a nonischemic control group (n = 6). At all [Ca]0, DP was depressed in the stunned group (P less than 0.001). Maximal Ca2+-activated pressure (MCAP), measured from tetani after exposure to ryanodine, was decreased after stunning (P less than 0.05). Normalization of the DP-[Ca]0 relationship by corresponding MCAP (Ca0 sensitivity) revealed a shift to higher [Ca]0 in stunned hearts. To test whether cellular Ca overload initiates stunning, we reperfused with low-[Ca]0 solution (0.1-0.5 mM; n = 8). DP and MCAP in the low-[Ca]0 group were comparable to control (P greater than 0.05), and higher than in the stunned group (P less than 0.05). Myocardial [ATP] observed by phosphorus NMR failed to correlate with functional recovery. In conclusion, contractile dysfunction in stunned myocardium is due to a decline in maximal force, and a shift in Ca0 sensitivity (which may reflect either decreased myofilament Ca2+ sensitivity or a decrease in the [Ca2+] transient). Our results also indicate that calcium entry upon reperfusion plays a major role in the pathogenesis of myocardial stunning.

Trousseau's syndrome. Devastating coagulopathy in the absence of heparin.

Two patients with Trousseau's syndrome experienced frequently recurring concomitant arterial and venous thrombotic events that resulted in sequential amputation and loss of the lower extremities. Serial examination of the blood in the patients demonstrated that these devastating thrombotic events were preceded by severe disseminated intravascular coagulopathy that occurred within an interval of a few hours. Warfarin therapy was without effect in preventing the occurrence of these events. Both patients demonstrated the absolute need for intravenous heparin, which effectively prevented the thrombotic events; when it was discontinued, the immediate consequences were disastrous and resulted in death. Techniques for long-term outpatient heparin therapy are discussed.

Esmolol versus verapamil in the acute treatment of atrial fibrillation or atrial flutter.

The effects of esmolol, an ultrashort-acting beta blocker, and verapamil were compared in controlling ventricular response in 45 patients with atrial fibrillation or atrial flutter, in a randomized, parallel, open-label study. Patients with either new onset (less than 48 hours, n = 31) or old onset (greater than 48 hours, n = 14) of atrial fibrillation or flutter with rapid ventricular rate were stratified to receive esmolol (n = 21) or verapamil (n = 24). Drug efficacy was measured by ventricular rate reduction and conversion to sinus rhythm. The heart rate declined with esmolol from 139 to 100 beats/min (p less than 0.001) and with verapamil from 142 to 97 beats/min (p less than 0.001). Fifty percent of esmolol-treated patients with new onset of arrhythmias converted to sinus rhythm, whereas only 12% of those who received verapamil converted (p less than 0.03). Mild hypotension was observed in both treatment groups. Esmolol compares favorably with verapamil with respect to both efficacy and safety in acutely decreasing ventricular response during atrial fibrillation or flutter. Moreover, conversion to sinus rhythm is significantly more likely with esmolol.

Pulmonary hypertension and interstitial fibrosis in von Recklinghausen neurofibromatosis.

Neurofibromatosis von Recklinghausen (NFvR) has been reported to be associated with diffuse interstitial pulmonary fibrosis. We describe a patient with NFvR presenting in middle age with dyspnea and cyanosis. Chest radiographs showed right ventricular enlargement, dilated proximal pulmonary arteries, and bilaterally increased interstitial markings. Cardiac catheterization showed moderately severe pulmonary hypertension and no evidence of congenital heart defect. The interstitial fibrosis associated with NFvR can result in symptomatic pulmonary hypertension.

Complete heart block developing during aortic valvuloplasty.

We report the occurrence of CHB consequent to ABV in an 80-year-old white woman with calcific aortic stenosis. The patient underwent ABV with a balloon 20 mm in diameter, resulting in only a modest increase in aortic valve area and a decrease in aortic valve gradient. The procedure was complicated by transient intermittent CHB which required temporary transvenous pacemaking and resolved within 72 hours. A second ABV was performed four weeks later with a balloon 23 mm in diameter. This was complicated by persistent CHB which required placement of a dual-chamber pacemaker.

Progressive hemochromatotic cardiomyopathy despite reversal of iron deposition after liver transplantation.

Dilated cardiomyopathy is a frequent and serious complication of idiopathic hemochromatosis. The mechanism by which disordered iron metabolism induces heart failure is not entirely understood, but myocardial dysfunction appears to be intimately related to the deposition of iron in myocytes. Cardiac function characteristically worsens or improves in proportion to the degree of iron accumulation in cardiac myocytes. The authors report the case of a 47-year-old man with idiopathic hemochromatosis and cirrhosis who developed symptoms of congestive heart failure and was found to have dilated cardiomyopathy 7 months after receiving a liver transplant. An initial endomyocardial heart biopsy demonstrated severe iron deposition in myocytes. The patient's heart failure worsened in the next 3 years and he eventually required a heart transplant. Examination of the explanted heart revealed dilated cardiomyopathy, but the previously demonstrated iron deposits in the cardiac myocytes were depleted. This "uncoupling" of cardiac function and cardiac iron load suggests that a threshold may be reached at which point the metabolic and ultrastructural derangements of iron deposition are no longer reversible, even with the removal of the inciting agent. Furthermore, displacement of myocyte iron stores after liver transplantation implicates altered hepatic iron metabolism as a primary or contributing mechanism in the pathophysiology of idiopathic hemochromatosis.

Contingent observation: an effective and acceptable procedure for reducing disruptive behavior of young children in a group setting.

Since a major task of childhood is learning to get along in a group without disrupting other children's activities, caregivers need explicit guidelines for gentle but effective procedures for dealing with disruptive behaviors in child-care settings. In a day-care center for normal 1- and 2-yr.-old children, an effort was made to develop a procedure that appeared sufficiently humane and educational to be acceptable to parents and day-care workers, and yet effective in reducing disruptive play behaviors. Caregivers used the occasion of disruptive behavior to instruct the child in appropriate alternatives, then had the child sit on the periphery and observe the appropriate social behavior of the other children "sit and watch", for a brief period before inviting him or her to rejoin the play activities. The effectiveness of this procedure was compared with a method commonly recommended for the use with young children: instructing the child, then distracting or redirecting the child to an alternative toy or activity. Contingent observation, combining instruction with a brief timeout (from being a participant in an activity to becoming an observer of the activity), proved considerably more effective in maintaining low levels of disruptions and was considered by caregivers and parents to be an appropriate and socially acceptable method of dealing with young children's disruptive behaviors. Therefore, contingent observation can be recommended for general use in day-care programs for young children.

Search and retrieval of a radiolucent foreign object.

Successful percutaneous removal of an intravascular foreign body requires precise localization of the object so that retrieval devices can be properly positioned. Here we report the successful search for and retrieval of a catheter embolus lost in the ascending aorta during PTCA whose localization was complicated because it was radiolucent.

Intracellular free calcium concentration measured with 19F NMR spectroscopy in intact ferret hearts.

Changes in the intracellular free Ca2+ concentration, [Ca2+]i, mediate excitation-contraction coupling in the heart and contribute to cellular injury during ischemia and reperfusion. To study these processes directly, we measured [Ca2+]i in perfused ferret (Mustela putorius furo) hearts using 19F NMR spectroscopy to detect the 5,5'-difluoro derivative of the Ca2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). To load cells, hearts were perfused with the acetoxymethyl ester derivative of 5,5'-F2-BAPTA. We measured 19F NMR spectra and left ventricular pressure simultaneously, at rest and during pacing at various external Ca concentrations [( Ca]o). Although contractile force was attenuated by the Ca2+ buffering properties of 5,5'-F2-BAPTA, the decrease in pressure could be overcome by raising [Ca]o. Our mean value of 104 nM for [Ca2+]i at rest in the perfused heart agrees well with previous measurements in isolated ventricular muscle. During pacing at 0.6-4 Hz, time-averaged [Ca2+]i increased; the effect of pacing was augmented by increasing [Ca]o. [Ca2+]i more than tripled during 10-20 min of global ischemia, and returned toward control levels upon reperfusion. This approach promises to be particularly useful in investigating the physiology of intact hearts and the pathophysiology of alterations in the coronary circulation.