Charles A. Sanders

The amount of left ventricular myocardium destroyed by recent and old infarcts in patients with acute myocardial infarction with and without cardiogenic shock was compared in hearts obtained at autopsy. All 20 patients with, and only one of 14 without, shock had lost 40 per cent or more of the left ventricle. The remainder lost 35 per cent or less. These results indicate that cardiogenic shock is associated with extensive loss of left ventricular myocardium due to new and frequently old infarcts as well. In five cases the new infarct was small as compared to the total amount of myocardial destruction. Patients with cardiogenic shock consistently showed marginal extension of the recent infarct (unlike those not in shock) and focal areas of necrosis throughout both left and right ventricles. Similar focal lesions were encountered in a third series of 20 patients with shock from other causes. A sharp reduction in coronary perfusion pressure could explain this combination of findings, which indicate that cardiogenic shock is a continuous, self-perpetuating, vicious circle leading to progressive, irreversible myocardial dysfunction.

BACKGROUND: Preclinical studies have demonstrated that nerve growth factor may prevent or reverse peripheral neuropathy. We have therefore tested the effects of recombinant human nerve growth factor in patients with diabetic polyneuropathy. METHODS: A total of 250 patients with symptomatic diabetic polyneuropathy randomly received either placebo or one of two doses of recombinant human nerve growth factor for 6 months. Patients were assessed for symptoms and signs of polyneuropathy before and after treatment. RESULTS: Compared with placebo, recombinant human nerve growth factor led to significant improvement after 6 months of treatment, as measured by the sensory component of the neurologic examination, two quantitative sensory tests, and the impression of most subjects that their neuropathy had improved. Three prospectively identified multiple endpoint analyses indicated improvements in the nerve growth factor treatment groups over the placebo group in all three analyses (p = 0.032; p = 0.008; p = 0.005). Recombinant human nerve growth factor was well tolerated, with injection site discomfort reported as the most frequent adverse event. CONCLUSIONS: Recombinant human nerve growth factor appears to be safe and shows preliminary evidence of efficacy in patients with symptomatic diabetic polyneuropathy.

The AVCO balloon pump has been employed in treating 40 patients with cardiogenic shock from acute myocardial infarction (CS-MI). All patients were given a trial of medical therapy with hemodynamic monitoring. The time from the development of shock to institution of intraaortic balloon pumping (IABP) was less than 24 hours in all but nine patients. Prior to IABP the mean hemodynamic values were: cardiac index (CI) 1.7 liters/min/m 2 ; mean arterial pressure (MAP) 66 mm Hg; pulmonary artery wedge pressure (PAW) 22 mm Hg. After 24-48 hours of IABP the CI and MAP had increased 0.8 liters/min/m 2 and 8 mm Hg, respectively, and the PAW had decreased 4.8 mm Hg. During IABP the shock syndrome was reversed in 31 patients. Four of 25 patients treated with IABP alone survived to be discharged, but two have died from subsequent infarctions. Because of the persistent high mortality, 15 patients judged unable to survive off IABP have undergone emergency surgical procedures with IABP continuing during preoperative angiography and postoperatively. Six were long-term survivors. It is concluded: (1) IABP is a safe, effective means of supporting the circulation in CS-MI; (2) IABP alone will improve survival in some patients; (3) IABP can provide circulatory support during angiography and the perioperative period in patients requiring revascularization for survival; and (4) some patients with CS-MI have myocardial necrosis too extensive to permit survival without permanent circulatory assistance or total cardiac replacement.

The effect of 0.3 mg sublingual nitroglycerin (NTG) was evaluated by hemodynamic measurements and precordial S-T-segment mapping in 17 patients following acute myocardial infarction. In all cases NTG produced a prompt reduction in mean pulmonary capillary wedge pressure (PCW) from an average of 19 ± 2 to 14 ± 1 mm Hg associated with a small fall in mean arterial pressure from a mean of 85 ± 4 to 82 ± 4 mm Hg. No significant change in heart rate occurred. In patients without left ventricular failure (PCW 3-12 mm Hg) cardiac output (CO) fell 9%. By contrast, in patients with moderate left ventricular failure (PCW 13-22 mm Hg) CO rose 18%. In three patients with refractory left ventricular failure (PCW 25-31 mm Hg) CO rose 25%. Two of these patients were treated with repetitive NTG doses in addition to previously ineffective diuretic therapy with resolution of resistant pulmonary edema. No significant changes in the magnitude of S-T-segment elevations were noted. NTG may have a special role in the management of acutely ill patients with myocardial infarction in whom pulmonary edema does not respond to conventional therapy.

Of 130 patients who received permanent pervenous pacemakers in the last 2 years at the Massachusetts General Hospital, 21 have died; complete postmortem data are available on seven who died 5 days to 18 months after insertion of the pacemaker. No deaths were related to pacemaker malfunction. No patient received routine anticoagulant therapy. The intracardiac portions of all pacemaker electrodes were 30 to 80% endothelialized. In three cases tiny, organized mural thrombi formed on these sheaths, but none appeared to give rise to pulmonary emboli. All pacemaker electrode tips were wedged firmly beneath the trabecular system of the right ventricular apex and elicited varying degrees of local fibrous tissue reaction. Further focal fibrotic attachments occurred in the right atrium and superior vena cava. Although in four cases the electrodes adhered to the chordae tendineae, the long-term presence of an electrode did not appear to compromise tricuspid valve function. Late removal of an electrode may be hazardous because of its firm attachments to the endocardium and tricuspid valve.