Pulmonary hypertension and cor pulmonale in the sickle hemoglobinopathies

Although pulmonary hypertension is frequently mentioned as a complication of the sicklemic state, careful review of the medical literature revealed only a single subject in whom cardiac catheterization data substantiated this diagnosis. In two additional patients, both clinical and autopsy findings of pulmonary vascular disease and cor pulmonale were described, although no hemodynamic studies had been performed. We have therefore detailed the clinical history, cardiac catheterization results, and autopsy findings in three previously undescribed patients. These three patients, along with the three case reports culled from the medical literature, form the substance of this review. Pulmonary hypertension should be suspected in patients with sickle hemoglobinopathy in whom either fixed dyspnea or unexplained syncope develops. Early in the course of the disease, right heart catheterization remains the only way to establish the diagnosis with certainty. Noninvasive studies such as chest x-ray, electrocardiography, and echocardiography tend to be nondiagnostic until late in the course of right ventricular failure. Although specific therapy has yet to be defined, the ominous prognosis of this complication of sickle hemoglobinopathy supports the application of experimental modalities such as continuous oxygen therapy, partial exchange transfusion, or even limited phlebotomy.     

Contractile and biochemical effects of coronary reperfusion after extended periods of coronary occlusion.

The effects of coronary reperfusion on recovery of regional myocardial contractility and high energy pegmental changes in myocardial contractility were measured by means of a strain gauge-tipped, two-pronged catheter probe that measures myocardial fiber shortening. The curves of contraction are sensitive to the effects of ischemia. Coronary occlusion resulted in a rapid replacement of fiber shortening by passive fiber lengthening. If coronary occlusion was released and blood flow restored within 45 minutes, myocardial contractility returned promptly; adenosine triphosphate and creatine phosphate values were restored to normal. With coronary occlusion of 1 hour or longer, contractility failed to return in the immediate postperfusion period, but delayed return was recorded after 2 weeks of reperfusion. The extent of such recovery varied with the duration of preceding occlusion. Thus, reperfusion after 1 hour of occlusion was followed by return of fiber shortening over the entire reperfused region. With 2 hours of occlusion, recovery occurred over 75 percent of the reperfused myocardium. With 3 hours of occlusion followed by reperfusion, recovery of contractility was only partial, comprising approximately 60 percent of the reperfused region. High energy phosphate content of the reperfused myocardium showed a similar pattern of recovery. With occlusion of longer duration, reperfusion failed to restore contractility to any significant extent. These findings indicate that reperfusion after coronary occlusion of 1 to 3 hours may restore contractility over a period of 2 weeks, but the extent of such recovery diminishes with the increase in the duration of occlusion.     

Therapeutic and clinical course of deep vein thrombosis

We have reviewed our experience with the treatment of 250 patients with deep vein thrombosis diagnosed by contrast venography. The level of thrombosis was recorded according to the anatomic level to which it extended. A third of the patients had cancer, and the most common clinical findings were swelling and pain. The risk of the development of pulmonary embolism, based on the anatomic level of initial deep vein thrombosis, revealed the following: 12 of 115 patients (10 percent) with level I (calf) deep vein thrombosis developed pulmonary embolism, as did 2 of 27 patients (7 percent) with level II (popliteal) disease, 5 of 60 (8 percent) with level III (thigh) disease, 1 of 19 patients (5 percent) with level IV (groin) disease, and 2 of 26 patients (8 percent) with level V (iliac) disease. Based on our favorable experience with heparin we believe that heparin is the treatment of choice for deep vein thrombosis regardless of the anatomic level. The incidence of pulmonary embolism does not appear to be influenced significantly by the level of the deep vein thrombosis.     

The role of calcitonin and parathyroid hormone in the pathogenesis of post-thyroidectomy hypocalcemia

Permanent hypocalcemia complicating thyroidectomy is a rare complication, whereas transient post-thyroidectomy hypocalcemia occurs frequently. Ten patients were studied in an attempt to elucidate the underlying mechanisms. An early and transient postoperative rise in calcitonin (CT) corresponding to a decline in calcium levels was demonstrated. Though there was no significant depression of parathyroid hormone (PTH) levels, the failure of the parathyroids to respond to hypocalcemic stimuli suggests a degree of at least transient parathyroid insufficiency. Transiently elevated CT levels appear to play a significant role in the commonly observed early, transient post-thyroidectomy hypocalcemia following subtotal and total thyroidectomy.     

Analysis of conduction velocity in the H pathway: Part 2. An electrophysiological study in diabetic polyneuropathy

The conduction velocity in the different partial segments of the monosynaptic pathway of the lower limbs has been assessed in 50 unselected diabetic patients in order to evaluate the distribution of conduction slowing in the entire course of peripheral nerves in the most common form of polyneuropathy.According to the method previously described (Troni 1981), the conduction velocity in the entire course (popliteal fossa-to-spinal cord), in the proximal segment (buttock-to-spinal cord) and in the distal segment (pf-to-buttock) of the H pathway, has been determined and expressed by mixed (sensory-motor) conduction indexes. Moreover, the conduction velocity of the la afferent and of the motor fibres, has been selectively evaluated in the pf-to-buttock segment.The comparison between the impairment of each partial conduction parameter proves the existence of a clear-cut proximo-distal gradient of conduction slowing in the H pathway in diabetic polyneuropathy.Marked slowing in the large-diameter la afferent fibres can also be demonstrated in the pf-to-buttock segment.     

Psychosocial disability during maintenance hemodialysis

Overall psychosocial functioning was assessed in 21 maintenance hemodialysis patients. The Ruesch Social Disability Scale, which provides an overall Social Disability (DS) score as well as subscores for Physical Impairment (PI), Behavioral Impairment (BI), and Social Modifiers (MS), was utilized. A majority of the patients (13) experienced Major Social Disability and the mean DS score of this sample was in the Major Social Disability range ($\text{x}$ = 52.1 ± 10.9). There were no differences between the mean DS score of men and women. Married patients had DS scores significantly lower than those who were divorced or never married (P < .05). Patients with more than five years of maintenance hemodialysis had a mean DS score significantly higher than those with less then five years of maintenance hemodialysis (P < .03). In those patients with more than five years of hemodialysis, the MS scale was significantly elevated (P < .01) in comparison with their counterparts, whereas the BI and PI scores were not different. The data suggest that serious psychosocial impairment is a common sequela of maintenance hemodialysis, especially for long-term patients and those who are not married. Therapeutic approaches directed toward improved social functioning are indicated.     

Activation of hepatic guanylate cyclase by nitrosyl-heme complexes: Comparison of unpurified and partially purified enzyme

The objective of this study was to evaluate the effects of several agents on activation of both unpurified and partially purified hepatic soluble guanylate cyclase by performed NO (nitric oxide or nitrosyl)-heme complexes. Guanylate cyclase was activated by NO complexes of the heme compounds, hematin, hemoglobin, myoglobin, catalase and cytochrome c, and also by the reaction product of NO and ferredoxin, a non-heme, iron sulfur electron transfer protein. NO-lipoxygenase, which contains non-heme iron, did not activate guanylate cyclase. NO-heme complexes activated unpurified enzyme almost equally well in the presence of either Mg²⁺ or Mn²⁺. However, activation of purified (350- to 750-fold) guanylate cyclase was markedly greater with Mg²⁺ than with Mn²⁺. At concentrations that did not alter basal enzymatic activity, Ca²⁺ markedly inhibited guanylate cyclase activation in the presence of Mg²⁺ but not of Mn²⁺. Hemoproteins inhibited activation of unpurified and purified enzyme by NO-heme complexes, and increasing the concentrations of the latter overcame the inhibition. Gel filtration studies indicated that uncomplexed and NO-complexed hematin bind to common or adjacent sites on guanylate cyclase. Whereas dl-dithiothreitol enhanced activation, ferricyanide, cystine, o-iodosobenzoic acid and ethacrynic acid inhibited activation of guanylate cyclase by NO-heme complexes. The data indicate that the effects of these diverse agents on guanylate cyclase activation by preformed NO-heme are similar to their effects on enzyme activation by NO and nitroso compounds, both of which readily form NO-heme complexes. Therefore, the effects of these diverse agents may be on guanylate cyclase rather than on NO-heme formation.     

Arrhythmogenic effects of carbon monoxide in experimental acute myocardial ischemia: Lack of slowed conduction and ventricular tachycardia

To investigate the possibility that carbon monoxide (CO) at high clinically encountered levels may have arrhythmogenic effect in initial minutes of acute myocardial ischemia, 14 dogs underwent thoracotomy and recording of bipolar epicardial electrograms during brief (6-minute) left anterior descending coronary artery (LAD) occlusions. Eight of the 14 dogs were studied both before and after CO pretreatment in which carboxyhemoglobin levels of 6.8% to 14.6% (mean 10.4 ± 2.8%) were achleved. Epicardial electrograms showed no change in degree of ischemic myocardial conduction slowing after CO, and there was no significant difference between CO and no-CO LAD occlusions in incidence of spontaneous ventricular tachycardia. Since the degree of myocardial conduction slowing is thought to be importantly related to susceptibility to ventricular arrhythmias in acute ischemia, this study suggests that CO may not be arrhythmogenic during early minutes of acute myocardial ischemia.