ATP compartmentation in neuroendocrine secretory vesicles.
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Biomedical subjects
Publications and source records attributed to R G Johnson.
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Coronary arterial pressure and flow are known to influence left ventricular (LV) diastolic distensibility, but the influence of coronary venous pressure is unknown. To test the hypothesis that increased coronary venous pressure leads to an increase in LV wall volume and a decrease in LV diastolic distensibility, we studied excised, blood-perfused LV isovolumic dog hearts without the pericardium. In protocol I (n = 8), to raise coronary venous pressure the pressure of right atrium (RA) and right ventricle (RV) was increased by the height of a blood reservoir connected with a cannula that opened in both the RA and RV. In protocol II (n = 7), to isolate the effect of RV enlargement on LV diastolic distensibility (direct ventricular interaction), an isovolumic RV balloon was used with coronary venous pressure held constant at 0 mm Hg. Changes in LV diastolic distensibility were assessed by shifts of the LV end-diastolic pressure-volume relation. Changes in LV wall volume were detected by subepicardial segment length at end-diastole. The mean pressures of RA and RV (protocol I) and RV balloon only (protocol II) were increased from 0 to 15 and 30 mm Hg over a range of LV volume. In protocol I, when RA.RV pressure was increased from 0 to 30 mm Hg at three levels of LV volume (22 +/- 2, 31 +/- 3, and 40 +/- 3 ml), LV end-diastolic pressures increased significantly from 5.2 +/- 0.3 to 11.2 +/- 1.5, from 10.4 +/- 0.3 to 18.2 +/- 1.2, and from 20.2 +/- 1.0 to 28.8 +/- 1.2 mm Hg, respectively. In protocol II, when RV balloon pressure was increased from 0 to 30 mm Hg at the three LV volumes (21 +/- 3, 31 +/- 3, and 41 +/- 4 ml), LV end-diastolic pressures showed smaller increases from 5.2 +/- 0.2 to 6.6 +/- 0.2, from 9.8 +/- 0.3 to 11.6 +/- 0.6, and from 19.0 +/- 0.5 to 21.4 +/- 0.8 mm Hg, respectively. In both protocols, the LV end-diastolic pressure-volume relation shifted upward in a nearly parallel fashion, but the shift was much greater in protocol I than in protocol II. Despite constant LV volume, an increase in LV wall dimension in protocol I was significant and much greater than that in protocol II. From these results, we conclude that increased coronary venous pressure decreases LV diastolic distensibility with increasing LV wall volume, and this mechanism appears to act independently of diastolic ventricular interaction caused by RV enlargement.
Novikoff hepatoma cells provide an excellent model system for the study of gap junction assembly, a process that could be influenced by lipids and other factors at numerous points. Since it is possible to alter the cellular levels of cholesterol in these cells, it was added to the cells in serum-supplemented medium and changes in gap junction assembly were evaluated. Cells were dissociated and reaggregated following exposure to a range of cholesterol concentrations for 24 h. A five- to sixfold increase in the number of aggregated gap junction particles and a 50% increase in cellular cholesterol content were observed with 20 microM added cholesterol. A 1-h exposure to added cholesterol, during cell reaggregation, resulted in a fourfold increase in the number of aggregated gap junction particles, demonstrating that the effect was rapid. The number of aggregated gap junction particles and formation plaque areas were used as measures of junction assembly and assayed by quantitative freeze-fracture and electron microscopy. Junctional permeabilities were evaluated by means of dye transfer times following the intracellular microinjection of Lucifer Yellow. Increased dye transfer was observed between cholesterol-treated cells, which suggested that the increase in assembly was accompanied by an increase in junction permeability. Cells were treated with cycloheximide (100 micrograms ml-1) and actinomycin D (10 micrograms ml-1) to determine whether protein and RNA syntheses were involved in the enhanced gap junction assembly. Cycloheximide but not actinomycin D blocked the increased junction assembly observed with added cholesterol. These results suggested that protein synthesis, but not RNA synthesis, is necessary for the increased gap junction formation observed.(ABSTRACT TRUNCATED AT 250 WORDS)
The effectiveness of desmopressin (1-desamino-8-D-arginine vasopressin) in reducing intraoperative blood loss during lumbar fusions was investigated in 42 patients (52 operations) and compared with a control group of 55 patients (63 operations). The mean hemoglobin and hematocrit levels on admission and discharge were identical for both groups. Patients receiving desmopressin required less than one-half the number of autologous transfusions than the control group. Desmopressin was effective in reducing blood loss in operations in which intraoperative bleeding was greater than 1,000 milliliters, but it is probably not necessary for anticipated losses less than this amount. It may have a role in operations performed on short notice when autologous blood is usually unavailable.
Of 2,102 consecutive patients who underwent percutaneous transluminal coronary angioplasty, 31 (1.5%) had emergency coronary bypass grafting for failed angioplasty. To determine the potential impact of different therapeutic strategies for controlling associated myocardial ischemia, 3 groups were analyzed. Group 1 comprised 11 patients (36%) in whom a "bailout" catheter was used to maintain anterograde coronary perfusion, group 2 included 16 patients (52%) in whom only intraaortic balloon counterpulsation was used and group 3 contained 4 patients (13%) in whom neither bailout catheter nor intraaortic balloon was used. Despite a longer average time to cardiopulmonary bypass, patients managed with the bailout catheter had a significantly lower incidence of Q-wave myocardial infarctions (9 vs 75%, p less than 0.05) compared with patients managed with intraaortic balloon counterpulsation alone. Those managed with the bailout catheter also had more consistent resolution of ST elevation and greater use of internal mammary artery grafts than patients supported by intraaortic balloon counterpulsation alone.
MP26, a protein thought to form gap junctional channels in the lens, and other lens proteins were phosphorylated under conditions that activate protein kinase C. Phosphorylation was detected both in lens fiber cell fragments in an "in vivo" labeling procedure with 32P-phosphate and in cell homogenates with 32P-ATP. In these experiments, both calcium and 12-O-tetradecanoylphorbol 13-acetate (TPA) were necessary for maximal phosphorylation of MP26. Calcium stimulated the phosphorylation of MP26 approximately fourfold and TPA with calcium led to a sevenfold increase. If TPA was present, 1 microM calcium was sufficient for maximal labeling. Phosphoamino acid analysis demonstrated approximately 85% phosphoserine, 15% phosphothreonine, and no phosphotyrosine when MP26 was phosphorylated in lens homogenates in the presence of TPA and calcium and then electrophoretically purified. Phosphorylation occurred near the cytoplasmic, C-terminal of MP26. The possible involvement of other kinases was also examined. The Walsh inhibitor, which affects cAMP-dependent protein kinases, had no influence on the TPA-mediated increase in phosphorylation. In studies with isolated membranes and added kinases, MP26 was also found to not be a substrate for calcium/calmodulin-dependent protein kinase II. Thus, protein kinase C may have phosphorylated MP26 in a direct manner.
Debridement of heavily calcified and adherent pericardium with an ultrasonic surgical aspiration device is described. The device proved to be a useful adjunct to the complete debridement of densely adherent pericardium.
This study was done to look for evidence of damage to a healthy disc resulting from diagnostic discography. Thirty-four patients had undergone a second discogram at 80 lumbar levels. There were 22 men and 12 women. The mean interval between discograms was 16.7 months (range, 3-38). Of 42 levels that were reported to be radiologically normal on the first discogram, ten were reported to be abnormal on the second discogram (24%). On review of these films, the abnormality was in fact present on the first discogram at two levels, and the second discogram was normal at two levels (radiologist error). Fusions had been done in three patients at adjacent levels between discograms. A compression fracture was present in adjacent vertebrae at two levels. Only one level was found to be truly abnormal on the second discogram for no obvious reason. The authors found no evidence that diagnostic discography damaged a normal disc.
Little is known regarding specific biologic and pharmacologic differences between human internal mammary arteries and saphenous veins. To better define the role of alpha-adrenoceptor-mediated vasoconstriction in human internal mammary arteries and saphenous veins, we obtained fresh specimens of both vessels from 32 patients undergoing coronary artery bypass surgery. Dose-response curves were generated for the relatively selective alpha 1-receptor agonist phenylephrine, the alpha 2-receptor agonist BHT-920, and the alpha 1- and alpha 2-receptor agonist norepinephrine. Phenylephrine elicited similar contractile responses in internal mammary arteries and saphenous veins, with a mean EC50 (the effective concentration necessary to produce 50% of the maximal contraction) of 1.4 X 10(-6) M for internal mammary arteries and 1.8 X 10(-6) M for saphenous veins (p = NS). Selective stimulation of alpha 2-receptors with BHT-920 elicited a marked contractile response only in saphenous veins. Dose-response curves for phenylephrine and BHT-920 were shifted to the right for both vessels in the presence of the alpha 1-receptor antagonist prazosin and the alpha 2-receptor antagonist yohimbine, respectively. Norepinephrine elicited contraction at a lower concentration in saphenous veins than in internal mammary arteries with a mean EC50 of 7.8 X 10(-8) M for saphenous veins and a mean EC50 of 3.4 X 10(-7) M for internal mammary arteries (p less than 0.05). The results suggest that alpha-adrenoceptor-mediated vasoconstriction is caused primarily by alpha 1-receptors in human internal mammary arteries and by alpha 1- and alpha 2-receptors in human saphenous veins.
To compare the effects of hypoxia and ischemia on left ventricular (LV) diastolic function, we studied 17 isolated, isovolumic dog hearts by measuring LV diastolic chamber distensibility (LV end diastolic pressure at constant volume), wall thickness, and myocardial pH in response to hypoxia at constant coronary flow or pressure versus global ischemia (zero coronary blood flow). Hypoxic perfusates consisted of methemoglobin-containing red blood cells suspended in lactated Ringer's solution. Brief cross-clamping of the coronary perfusion line was used to assess the contribution of coronary turgor to chamber distensibility and wall thickness. With hypoxia, left ventricles showed a significant early (5 minutes) decrease in diastolic distensibility and an increase in wall thickness, at either constant coronary perfusion pressure or flow. The increase in wall thickness was independent of hypoxia-induced changes in coronary turgor. In contrast, global ischemia produced an early increase in LV diastolic chamber distensibility and a decrease in wall thickness. When global ischemia was continued beyond 60 minutes, a decrease in LV chamber distensibility developed. This diastolic contracture was not associated with an increase in LV wall thickness. Myocardial pH decreased slightly during 15 minutes of hypoxia and markedly with 15 minutes of global ischemia. Thus, LV diastolic chamber distensibility decreased during 15 minutes of hypoxia, while an increase in distensibility was seen during global ischemia of similar duration. During hypoxia, these changes were associated with increased LV wall thickness, at either constant coronary perfusion pressure or constant coronary flow. Prolonged ischemia led to diastolic contracture without an increase in wall thickness.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood losses and transfusions have been analyzed prospectively for 63 lumbar fusion operations in 55 patients. The mean intraoperative loss was 550 ml, with a further 336 ml in postoperative drains. Factors increasing intraoperative loss included posterior vs. anterior approach, the use of instrumentation, multiple levels fused, male vs. female, and younger age. For anterior procedures (without instrumentation and using homograft bone) and single-level posterolateral fusions (PLF) without instrumentation, neither predeposit nor intraoperative salvage (cell saver) was required. Single-level PLF with instrumentation and two-level PLF without instrumentation required either cell saver or predeposit of one or two units. Multiple-level PLF with instrumentation and all 360 degrees procedures required cell saver and two units of predeposit. Two patients received homologous blood.
Postoperative analgesia using continuous epidural morphine or a single intrathecal injection of morphine has been compared with standard patient-controlled analgesia (PCA) in lumbar fusion patients. Pain relief with epidural morphine was dramatic in some cases (3/12) but was not predictable, and catheter displacement was a frequent occurrence. A single intrathecal bolus of morphine had no advantage over PCA alone. Complications of both intraspinal techniques included nausea and pruritus. No respiratory depression was observed.
A case of sternal dehiscence repaired with a Harrington compression system is presented. This is a widely available apparatus, is relatively simple to use, and provides rigid internal fixation.
We present preliminary details of the changes that occur in a new model for the study of degenerative arthritis which does not involve intraarticular surgery. A unilateral valgus tibial osteotomy was performed in a group of 8 skeletally mature dogs of mixed breed and sex. Proximal tibial cartilages, femoral condyles and patellas were examined in operated and unoperated knees of experimental and unoperated dogs. Lesions were examined histologically and analyses were made of 35SO4 uptake and uronic acid content as measures of proteoglycan synthesis and content, respectively. Water contents were also determined. Dogs were examined from 22 to 62 weeks after osteotomy. Angulation induced by the osteoarthritis was varied from animal to animal in this preliminary study. Histologically, degeneration of the patella was observed in 3 of 5 experimental dogs and in both operated and unoperated limbs in two of the dogs. Lesions were seen in both limbs and were most common in the tibial plateau where they were present both in the lateral (covered by meniscus) and medical (uncovered) compartments of the operated and unoperated limb. In the tibial plateau initial increases in proteoglycan content and synthesis were recorded in both limbs: later after 30/36 weeks these declined to normal. In the femoral condyles, increases in water content with angulation were seen in the lateral and medial condyles of operated limbs and in the medial condyles of unoperated limbs. Other changes in proteoglycan content were observed in both condyles with a loss of proteoglycan with increased angulation being recorded in the lateral condyle of the operated limb and an increase in proteoglycan with angulation in the medial condyle of the unoperated limb. These early changes are presumably in response to alterations in load bearing in both limbs. CLINICAL RELEVANCE. This study permits an analysis of degenerative changes that can occur when articulation is changed by an osteotomy. Since the changes occur in both limbs, are potentially reversible and are induced by extraarticular surgery, we have an attractive new model for studying degenerative arthritis.
This is a report of 85 patients who underwent anterior lumbar interbody fusion (ALIF) for treatment of painful disc disruption (PDD) or symptomatic pseudarthrosis. The fusion rate was 80% by disc. The pseudarthrosis rate increased from 16% at L5-S1 to 21% and 31% at L4-5 and L3-4, respectively. There was a significant increase in pseudarthrosis rate in patients who smoked more than one pack per day. There was no difference in the fusion rate whether autogenous or cadaveric iliac crest graft or dowel versus tricortical block graft was used. Sixty-eight percent of patients were "able to work" after ALIF. The complication rate was low and retrograde ejaculation occurred in only one patient.
Proplast reconstruction of iliac crest defects resulting from bone grafts taken for anterior lumbar and cervical fusions is described. The procedure improves the cosmetic result, prevents postoperative muscle herniation and may decrease postoperative donor site pain. It is a simple procedure with low complication rate when performed in the manner described.
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Intravenous digoxin, 1 mg, was administered over 8 hours to 10 cardiac patients with left ventricular (LV) dysfunction after coronary artery bypass grafting. The cardiovascular effects of digoxin were monitored over 20 hours by indwelling pulmonary artery and radial artery lines and were compared with those of a control group of 10 patients who had normal postoperative LV function. Digoxin administration produced an increased cardiac index and mean arterial blood pressure within 2 hours. Within 4 hours after digoxin administration pulmonary artery wedge pressure in patients receiving digoxin was significantly lower than in control patients. At 16 hours there was a significant increase in both the LV stroke work and LV stroke work index in patients receiving digoxin vs control patients. Two patients receiving digoxin and 3 control patients had changes in cardiac rhythm during the study. Thus, digoxin can be safely administered to postoperative patients with LV dysfunction and is an acceptable inotropic agent.