Walter M. Whitehouse

Back-diffusion of CO2 and its influence on the intramural pH in gastric mucosa

We have examined the back-diffusion of CO2 generated by buffering HCI with NaHCO, in the stomach, observed its influence on the pH in the wall of the gastric mucosa, and compared its effects with those of HCl. Isolated stomachs of 17 anesthetized dogs were exposed to either ( I ) 250 ml NaCl at pH 7, or (2) 125 ml HCl (12.5 meq) + 125 ml NaHCO, (12.5 meq) to generate 12.5 meq CO2 in the stomach, or (3) 250 ml HCI alone to give either 12.5 or 35 meq HCl in the stomach. Samples of gastric fluid and arterial blood were collected every 20 min for 6 hr and analyzed for pH and pC02. The intramural pH of the gastric wall was measured by hollow viscus tonometry. The pC02 in gastric juice rose to 1184 + 139 mm Hg upon the generation of CO2 in the stomach. The till of the CO2 generated by the buffering of acid was 32 + 4 min and of the pC02 was 18.7 f 0.7 min. The till of an equimolar amount of HCI was 2 hr 42 min f 40 min. The disappearance of the CO, was accompanied by a rise in intragastric pH from 6.0 f 0.01 to 6.8 + 0.09 (P < 0.05). and by a fall in intramural pH in the gastric wall from control values of 7.31 + 0.05 to 6.3 f 0.8 (P .Z 0.001). In contrast the pH in gastric fluid did not change and the pH in the intramural fluid did not fall below control values following the administration of 12.5 or 35 meq HCI alone.

Celiac artery aneurysms: Historic (1745-1949) versus contemporary (1950-1984) differences in etiology and clinical importance

Celiac artery aneurysms were encountered in nine patients, ranging in age from 39 to 76 years, at the University of Michigan Medical Center between 1961 and 1983. Developmental defects and atherosclerosis were etiologic factors in six cases. Four patients were without symptoms, whereas five experienced abdominal pain, including one with a ruptured aneurysm. Eight patients were subjected to surgical treatment; no deaths occurred and symptoms were resolved in all patients. A literature review of 108 celiac artery aneurysms revealed two distinct subgroups. Among 60 celiac artery aneurysms encountered before 1950, representing the historic era, 40% were infectious (usually luetic), 7% were traumatic, and 52% were of undetermined cause. Most were symptomatic, 87% ruptured, and 95% were diagnosed at postmortem examination. The contemporary era since 1950 consisted of 48 cases, including nine in the Michigan experience. Congenital or developmental medial defects of the arterial wall and atherosclerosis were the most common causes of aneurysms. Most aneurysms in the contemporary period were either asymptomatic or accompanied by vague abdominal discomfort. Rupture affected 13% of those aneurysms. Operative therapy was successfully undertaken in 91% of 43 patients during the contemporary era, including eight in the present series.

Atherosclerotic extracranial carotid artery aneurysms.

Twenty-four atherosclerotic extracranial carotid artery aneurysms were encountered in 21 patients during a 25-year period. These represented 46% of all extracranial carotid artery aneurysms diagnosed at the University of Michigan during this period. Neurologic symptoms including amaurosis fugax, transient ischemic attacks, and stroke were present in 50% of the patients. An asymptomatic pulsatile neck mass occurred in 33%. Surgical therapy was undertaken for 18 aneurysms, and nonoperative treatment was pursued in the remaining six aneurysms. Operative therapy included 14 aneurysmectomies and four aneurysmorraphies. There were no surgical deaths. Transient perioperative neurologic deficits affected three of these patients (17%), and one individual (5%) experienced a permanent deficit. Transient cranial nerve deficits occurred in three patients (17%), and a permanent deficit was noted in one patient (5%). During a 7.6-year follow-up period no late strokes occurred among patients who were operated on. Nonoperative therapy was associated with three ipsilateral strokes during a mean follow-up period of 6.3 years. Atherosclerotic extracranial carotid artery aneurysms were associated with an exceptionally high stroke rate (50%) if treated nonoperatively. Prevention of late stroke justifies surgery, although perioperative neurologic deficits may accompany this therapy more often than with nonatherosclerotic carotid artery aneurysms.

Pulmonary and pleural lesions in rheumatoid disease.

Pulmonary and pleural lesions are not uncommon in rheumatoid disease. Nonspecific pleuritis is a frequent finding at necropsy (1, 2), and rheumatoid nodules of the pleura have been observed (3–5). Such nodules have been described in the lungs of coal miners with rheumatoid disease (Caplans syndrome) (6–8) and in patients with other forms of pneumoconiosis (9–11). In addition, rheumatoid nodules have occasionally been reported in the lungs of patients who had not had such occupational exposures (12–15). In 1943 Ellman and Ball (16) called attention to diffuse pulmonary fibrosis at necropsy in two rheumatoid patients, and subsequently many similar cases were described. The recognition that clinical manifestations may occur with such pulmonary involvement led to the concept of the “rheumatoid lung syndrome.” This concept has not gained universal acceptance largely because of the nonspecificity of some of the pulmonary and pleural changes and the considerable variation in the type of involvement encountered....

The effect of protamine sulfate on platelet function

The adverse effects of protamine sulfate, used to neutralize the anticoagulant action of heparin, include systemic hypotension, pulmonary artery hypertension, thrombocytopenia and leukopenia. For further evaluation of protamines mechanism of action, a three-part investigation was performed. In part I platelet-rich plasma (PRP) was prepared from canine blood samples (n = 6) taken before and 2 minutes after injection of protamine. In part II human PRP (n = 5) was preincubated with protamine or distilled water. Adenosine diphosphate-induced aggregation of protamine-treated platelets was unchanged, but thrombin-induced aggregation was inhibited in both canine and human preparations (p less than 0.05). In part III thrombocytopenia was produced in splenectomized dogs (n = 5), using microporous filters, to 4.5-8.4% of the initial platelet count. Protamine reversal of the heparinization caused hypotension (maximally -29 mmHg 90 s after protamine), but not pulmonary arterial hypertension. Leukopenia developed before additional thrombocytopenia appeared. Protamine-platelet interaction inhibits thrombin-induced platelet aggregation. Platelets may play an important role in the pulmonary pressure rise during protamine reversal, but do not mediate the systemic hypotension.

Developmental occlusive disease of the abdominal aorta and the splanchnic and renal arteries

Developmental occlusive disease of the abdominal aorta and the renal and splanchnic arteries represent an unusual vascular condition. When unrecognized or untreated this disease is associated with premature death, usually from severe secondary hypertension as a consequence of renovascular stenotic lesions. Strong circumstantial evidence indicates that developmental abnormalities occurring during the fetal union of the two dorsal aortae account for most of the occlusive lesions affecting the abdominal aorta and its visceral branches in these patients. Complete arteriographic studies are necessary to confirm and accurately delineate the disease process. Surgical treatment, which often encompasses complex vascular reconstructive efforts, affords excellent results when carefully planned and executed.

Depressed cardiovascular function and altered platelet kinetics following protamine sulfate reversal of heparin activity.

This investigation documented the hemodynamic effects of rapid intravenous and intra-arterial administration of protamine sulfate, altered platelet kinetics associated with intravenous protamine sulfate administration, and a possible method of reducing protamine sulfate-induced hypotension. Thirty-six anesthetized dogs underwent continuous hemodynamic monitoring prior to heparinization (150 U/kg) and for 30 minutes after rapid reversal with protamine sulfate (1.5 mg/kg over 10 seconds). Platelet counts, platelet aggregation, and serum thromboxane B2 levels were also assessed. Intra-arterial protamine sulfate administration caused fewer adverse hemodynamic changes than intravenous administration, including significantly (p less than 0.05) reduced falls in mean arterial pressure (-10 vs. -35 mm Hg), cardiac output (-0.2 vs. -0.6 L/min), femoral artery blood flow (+ 34 vs. -16 ml/min), and superior mesenteric artery flow (+ 107 vs. -48 ml/min). Thrombocytopenia following protamine sulfate administration was the same in the two groups. Marked hypotension accompanying intravenous protamine sulfate administration was completely attenuated by a small dose of protamine sulfate (0.75 mg/kg) administered prior to heparinization. Similarly, the thrombocytopenia caused by intravenous administration was significantly lessened by protamine sulfate pretreatment (74% vs. 23% reduction; p less than 0.01). These observations have important implications for both experimental and clinical use of heparin and protamine sulfate.

Protamine reversal of anticoagulation achieved with a low molecular weight heparin. The effects on eicosanoids, clotting and complement factors

Hemodynamic and hematologic effects of protamine reversal of low molecular weight heparin (LMWH) anticoagulation with and without protamine pretreatment, as well as reversal of anticoagulation with unfractionated standard heparin (SH), were studied in canine subjects. Protamine reversal caused less severe thrombocytopenia in the two LMWH groups compared to SH animals, while neutropenia occurred equally in all groups. Cl-esterase inhibitor levels were minimally increased, whereas C3 levels and leucotriene levels were unaltered. TxB2 and 6-keto-PGF1 alpha increased during protamine reversal of LMWH anticoagulation. TCT and APTT were affected less with LMWH than SH anticoagulation. Anti-Xa levels increased with anticoagulation in all animals, but protamine did not reverse the elevated anti-Xa levels in LMWH anticoagulated dogs to the same degree as occurred with SH anticoagulation. TCT, APTT and bleeding times were normalized by protamine in all animals. Protamine reversal of LMWH anticoagulation with or without protamine pretreatment did not reveal any clear differences in eicosanoids or complement factors compared to SH anticoagulation, although differences in anti-Xa activity clearly separated these two heparins.

Management of iatrogenic arterial injuries in infants and children

Thirty-two patients with 33 suspected iatrogenic arterial injuries were evaluated from 1974 to 1982. Their mean age was 2.5 yr. Twenty-one injuries occurred after angiography and 7 followed umbilical artery catheterization. Of 5 clinical features of patient presentation, only the Doppler ultrasound examination permitted distinction of mechanical from functional arterial obstruction, detecting 92% of the mechanical obstructions. Twenty-one (64%) of the injuries were thought due to mechanical obstruction and 18 of these were due to thrombosis. Twelve injuries were due to spasm and were completely reversed without operation. Tissue loss occurred in 6 (18%), only 1 of whom received intravenous heparin. There were 7 deaths, 4 related to the vascular injury. Results in the first week after injury were excellent or acceptable in 74% of all injuries and 90% of those following angiography. Eight of 10 children (80%) treated with heparin had an acceptable or excellent late result, while only 9 of 16 children (56%) treated without heparin had acceptable or excellent results. Six early operations were performed; 4 were thrombectomies of which 2 were successful. Five late operations were performed, of which 2 resulted in correction of leg length discrepancy and 1 in relief of claudication. There were no complications of heparin therapy. We conclude that if there is no early return to normal clinical examination after a suspected iatrogenic arterial injury in an infant or young child, intravenous heparin therapy should be instituted. If the Doppler examination is not normal after 48 hr, thrombectomy should be pursued in otherwise well patients. If thrombectomy fails or if the child is seriously ill, continued observation is reasonable. Long-term follow-up should include scanograms for following leg length discrepancy. If aortic obstruction is suspected, early operative intervention may improve currently poor results.

Reoperation for complications of renal artery reconstructive surgery undertaken for treatment of renovascular hypertension

Seventy-two secondary operations for complications of prior renal artery reconstructive surgery were undertaken in 58 patients. This experience evolved from the management of 373 patients who underwent 425 primary operations for renovascular hypertension. Secondary operations were performed 10 times in pediatric patients following 42 primary procedures (24%); 44 times in adult fibrodysplastic patients following 199 initial operations (22%); and 18 times in atherosclerotic patients after 184 primary operations (10%). The overall reoperation rate was 15.5% (58 of 373 patients). Reoperation typically followed persistent or recurrent hypertension caused by graft thromboses, perianastomotic graft narrowing, or progressive nonanastomotic graft stenoses. Aneurysmal deterioration of vein grafts was an uncommon reason for reoperation. Secondary reconstructions included nephrectomy (31), bypass with vein grafts (15) or prosthetic grafts (8), angioplasty or reimplantation (12), thrombectomy (4), and operative dilation (2). Benefits regarding hypertension control were afforded 91% of these patients. One death occurred among the 72 reoperations, representing a 1.4% operative mortality rate. Reoperative renal artery reconstructive surgery for complications of renal revascularization may present formidable technical problems. Early diagnosis and prompt reoperation with exacting vascular surgical techniques are most likely to provide optimal results.