Chronic pernio. A historical perspective of cold-induced vascular disease.

Chronic pernio, or cold-induced vascular disease, is an uncommon syndrome with a clinical resemblance to vasculitis or peripheral cholesterol embolization. We studied a case of chronic pernio in which the angiogram revealed extensive vascular changes indistinguishable from vasculitis; pathologic studies of previously reported cases have revealed a primary vasculopathy. The pathophysiology of chronic pernio may be cold-induced vessel damage leading to a secondary dermopathy. Our patient's condition improved once the correct diagnosis was established and appropriate therapy was instituted.

Adrenal imaging with 131I-19-iodocholesterol in the diagnostic evaluation of patients with aldosteronism.

The results of adrenal scintiscans, venograms and venous aldosterone levels are compared with the histologic findings in 33 patients submitted to operations for primary aldosteronism. Standard and suppression scintiscans were performed 2-14 days following intravenous administration of 2mCi of 131I-19-iodocholesterol. The adrenal lesions were histologically classified into four categories: 25 patients had adenomas, 6 had macronodular hyperplasia, 1 had microscopic hyperplasia and 1 had an adenocarcinoma. Asymmetrical uptake between the two adrenals seen on standard scintiscans did not differentiate between a tumor or asymmetrical hyperplasia, unless the tumor was greater than 2 cm in diameter. During suppression scintiscans, unilateral uptake visible within five days of tracer injection was consistent with adenoma. Patients with nodular hyperplasia demonstrated early uptake in both adrenal glands during suppression scintiscans, while the patient with microscopic hyperplasia did not. The type of adrenal lesion was correctly identified in 20/26 (77%) of patients by suppression scintiscans; 21/28 (75% of patients by venograms and 12/16 (75%) of patients who had adrenal venous aldosterone measurements attempted. The majority of surgically correctible lesions could be identified on suppression adrenal scintiscans. Adrenal vein catheterization can be reserved for those patients in whom the results of suppression scintiscans are inconsistent with the clinical degree of aldosteronism.

Hypothenar hammer syndrome. Form of reversible Raynaud's phenomenon.

Hypothenar hammer syndrome is a reversible yet uncommonly encountered cause of Raynaud's phenomenon. Characteristic findings include coldness in the dominant hand of a male, absence of triphasic color change and thumb involvement, and occupational or recreational use of the hand as a hammer. Angiography demonstrates the specific findings of irregularity or occlusion of the ulnar artery, downstream occluded proper digital arteries, and intraluminal emboli at the sites of distal obstruction. A vulnerable area of traumatic occlusion is provided by the anatomic relationship of the superficial branch of the ulnar artery to the hamate bone and the palmar aponeurosis. Pathologic studies separate the hypothenar hammer syndrome from clinically similar vasculitis. It is important to recognize the hypothenar hammer syndrome as a distinct entity because treatment is curative and consists of resection of the affected vascular segment and avoidance of the aggravating conditions.

The role of bronchial arteriography and therapeutic embolization in hemoptysis.

A case is presented which demonstrates the value of bronchial arteriographic studies in localizing and treating hemoptysis. The patient was bleeding from an old post-tuberculous bulla and for several reasons was not a candidate for surgery. Bronchial arteriographic studies demonstrated both hypervascularity in the region of the cavity and also a mycotic aneurysm of a bronchial artery. After therapeutic embolization with gelatin (Gelfoam), the hypervascularity and aneurysm were no longer opacified. Active bleeding abruptly ceased and, except for a single mild recurrence, has not recurred during the three months since therapeutic embolization. The major theoretic risk of bronchial arteriographic study and therapeutic embolization is spinal injury. It is believed that permanent injury can almost be avoided, providing proper technique is used.

Non-occlusive ischemic colitis: angiographic aspects in a canine model.

A model of non-occlusive colonic ischemia (NCI) was produced in the dog, incorporating both moderately decreases systemic pressure and increased intralumenal colonic pressure. These factors may play an etiologic role in human NCL. When differences between mean systemic and mean distention pressures were 30 mmHg or less, severe mucosal injury occured. In no case was the muscularis injured. Moderate systemic hypotension alone, or moderate colonic distention alone, did not produce significant colonic ischemic injury. Colonic distention with pressures of 60 mmHg alone resulted in colonic mucosal necrosis, but these pressures are beyond those ordinarily encountered clinically, even in large bowel obstruction. Angiography may be useful in demonstrating reduced flow to the colon during development of colonic ischemic injury. However, angiography is not a sensitive method in the diagnosis of nonocclusive colonic ischemic injury, once that injury has been established and inciting factors have subsided.

Accelerated thrombolysis. In vitro evaluation of agents and methods of administration.

Three groups of experiments were conducted in vitro to determine the relative rates of thrombolysis produced by current clinically-relevant concentrations of streptokinase (SK), urokinase (UK), tissue-type plasminogen activator (t-PA), and plasmin; the concentration-response curves for each agent; and the advantages of mechanical admixture of fibrinolytic agents over simple soak. For Group 1 and 2 experiments, thrombolysis was quantitated by weighing freshly prepared clots before and after 2-hour fibrinolytic soaks. For experiments in Group 3, radio-labeled fibrinogen clots were used, and the amount of lysis was determined by measuring radioactivity in residual clot and supernatant fluid. Results indicated that SK, UK, plasmin, and t-PA in saline all produced roughly equivalent rates of lysis at molarity of 10(-6). Concentrations of SK above this level (corresponding to above 5000 units/ml) slowed lysis markedly; progressively increasing concentrations of UK and t-PA produced faster lysis, with slope of about 17 and 37%, respectively, per log10 of concentration. The efficacy of fibrinolytic agents was significantly enhanced by admixing clot and agent, using intrathrombic injections or clot maceration. With clot volumes of 0.5 ml, residual clot was frequently only 1/2 to 1/3 as much from macerated clots as from clots that were soaked whole. With the further addition of intrathrombic plasminogen, lysis was nearly completed after 30 minutes.

Comparative efficacy of coronary vasodilatory methods.

The relative efficacy and sequelae of several coronary vasodilator methods were compared in dogs. Maximal coronary vasodilation with least apparent side effect was achieved with infusion of adenosine triphosphate (ATP) at the rate of approximately 600 microng/minute (approximately 20 microng/kg/minute). This method increased conductance to 7 to 8 times control levels and may have fully depleted vasodilator reserve. Bolus injections of ATP or papaverine alone increased conductances three to four fold and approximated the effects of 15 seconds of occlusion of the circumflex coronary artery. Duration of effect was variable. Diatrizoate injections were somewhat less effective vasodilators and produced greater electrocardiographic and systemic effects. Bolus injections of mixtures of ATP and papaverine demonstrated additive effects, and increased conductance 5 to 6 times control levels. In further exploring the diagnostic value of vasodilatory redistribution of myocardial blood flow or appearance of collateral circulation as a sign of a hemodynamically significant stenosis, selective intracoronary infusion of ATP is a promising vasodilatory method.

Fibrinolysis with intrathrombic injection of urokinase and tissue-type plasminogen activator. Results in a new model of subacute venous thrombosis.

The efficacy of intrathrombic deposition vs. parathrombic infusion of urokinase (UK) and tissue-type plasminogen activator (t-PA) was investigated in a canine model. Gianturco coils were placed by transcatheter techniques into the iliac veins of 12 dogs. Venography obtained 48 hours later showed formation of large thrombi. After heparinization, UK (24,000-48,000 IU/ml) or t-PA (12,500-25,000 IU/ml) was spray-injected at high pressure throughout test clots every half-hour using a steel catheter with multiple side holes. Between injections, the agent was infused below the clots. The contralateral thrombi received an equivalent dose of fibrinolytic agent by continuous infusion. In six cases, plasminogen was injected into test clots prior to activator treatment. Thrombi spray-injected with either activator lysed in 64 +/- 26 minutes. Four of six thrombi treated with parathrombic urokinase infusion showed partial lysis after 133 +/- 50 minutes. After parathrombic infusion of t-PA, three clots showed complete lysis, one showed partial lysis, and two demonstrated no lysis. There was no significant difference in lysis rate between intrathrombic UK and t-PA nor did prior intrathrombic injection of plasminogen accelerate lysis. In summary, intrathrombic injection of highly concentrated UK or t-PA lysed subacute thrombi more effectively than parathrombic infusion.

Efficacy of adjunctive intrathrombic heparin with pulse spray thrombolysis in rabbit inferior vena cava thrombosis.

RATIONALE AND OBJECTIVES: The efficacy and speed of pharmacomechanical thrombolysis may be limited by thrombotic effects of activated platelets and thrombin within the lysing clot. The authors designed an animal model of subacute venous thrombosis which was used to evaluate the effect of intrathrombic versus intravenous heparin during thrombolysis. METHODS: Inferior vena cava (IVC) thrombosis was induced in rabbits by balloon catheter injury and placement of steel coils. Venacavagrams were obtained 48 hours later to document clot formation and for angiographic estimation of clot volume. Pulse-spray thrombolysis was performed by forceful injections of various agents through a catheter with multiple side holes spanning the clot. Most animals were given aspirin (30 mg orally) before treatment. After 1 hour of therapy, repeat venacavography was performed. Animals were killed, and residual clot weight was determined. RESULTS: Occlusive IVC thrombi were present in 94% of rabbits at 2 days. Mean residual clot weight per milliliter of estimated initial clot volume (mg/mL) for the various treatment groups was as follows: saline (n = 5) 632 +/- 54; tissue-type plasminogen activator (t-PA) 3 mg, (n = 6) 443 +/- 162; t-PA 3 mg + heparin 750 U intravenously, (n = 7) 408 +/- 128; t-PA 3 mg + heparin 500 U intrathrombic + heparin 250 U intravenously, (n = 8) 213 +/- 166. Differences among these groups (except t-PA alone versus t-PA + intravenous heparin) were significant. The extent of lysis with intrathrombic + intravenous heparin was not significantly retarded by withholding aspirin (n = 6, 194 +/- 72), or improved by giving half the intrathrombic heparin before t-PA injections (n = 6, 280 +/- 158). CONCLUSIONS: The results demonstrate the advantage of adjunctive intrathrombic + intravenous heparin over intravenous heparin alone in increasing the extent of pulse-spray thrombolysis in this IVC thrombosis model.

Comparative hemodynamic effects of coronary vasodilators and contrast material on the normal and ischemic canine myocardium: determination of the optimal agent for clinical augmentation of coronary blood flow.

The systemic hemodynamic and myocardial effects of potent vasodilators administered directly into the left coronary artery were determined and compared with the actions of contrast material in 10 anesthetized dogs in the normal state and in the presence of segmental myocardial ischemia. Contrast material (Renografin 76) caused systemic hypotension, rise in left ventricular diastolic pressure and decreases in LV dp/dt and dp/dt/LVP in both states. Doses of ATP (7.2 microgram/kg and 20 microgram/kg/min) which are maximally effective in augmenting coronary blood flow caused only mild arterial hypotension and minimal inotropic effects in both states. Nitroglycerin (3 microgram/kg and 10 microgram/kg/min) induced no inotropic effects but slightly greater arterial hypotension than ATP in both states. On the other hand, papaverine HCl (300 microgram/kg and 800 microgram/kg/min) induced profound increases in LV dp/dt and dp/dt/LVP, decreases in LVEDP and arterial hypotension in the non-ischemic state. In the presence of segmental ischemia, papaverine HCl caused significantly less increases in LV dp/dt and dp/dt/LVP, paradoxical increases in LVEDP in 5 dogs and ventricular fibrillation in 3 dogs. Thus, maximally effective vasodilatory doses of ATP causes only small alterations in hemodynamics and myocardial contractile state of the normal and ischemic heart. Similar doses of papaverine induce profound positive inotropic effects which are apparently deleterious to the ischemic heart.

The cavernosal acetylcholine/papaverine response. A practical in vivo method for quantification of endothelium-dependent relaxation. Rationale and experimental validation.

An in vivo method has been developed for quantifying cavernosal endothelium-dependent relaxation. The method is based on the fact that relaxation of the smooth muscle around the sinusoids of the penile corpora cavernosa activates the erectile veno-occlusive mechanism, and the degree of veno-occlusion can be precisely quantified by the pharmacologic maintenance erectile flow (PMEF) method. Pharmacologic maintenance erectile flows are determined after intracavernosal infusion of the endothelium-dependent relaxant acetylcholine (ACh) and the endothelium-independent relaxant papaverine, and expressed as an acetylcholine/papaverine ratio (APR). Control rabbits showed no changes from the test procedures themselves. In 12 test rabbits, control PMEFs after approximately 10(-7) mol ACh or papaverine averaged 0.7 and 0.5 ml/minute, respectively; APR averaged 1.3. Endothelial injury of the corpus cavernosum was produced by intracavernosal injection of 100 micrograms (16 x 10(-8) mol) of the detergent CHAPS or 1 ml of Renografin-76. Within 1 hour of injection of either agent, PMEF(ACh) increased markedly to approximately 6, PMEF(pap) increased minimally to approximately 0.9, and APR increased to about 7. These values gradually decreased to normal limits at six weeks. Endothelial injury and recovery were confirmed by electron microscopy. Thus, reduced cavernosal response to ACh relative to papaverine was indicative of endothelial injury. The ACh/papaverine response ratio offers promise as a practical and reliable in vivo method for quantifying endothelial-dependent relaxation.

The effect of vasospasm on perfusion radionuclide imaging in experimental pulmonary embolism.

Experiments were conducted to further evaluate previously observed discrepancies between postembolic perfusion scans and angiograms, and the relationship of these discrepancies to pulmonary vasospasm. Nonresorbable emboli were formed from Ivalon, muscle, or heated autologous clot. Scans and angiograms were compared at 24-hour intervals for two to eight days. During the first two days after embolism, angiographic-scan discrepancies occurred in most dogs, characterized by decreased size of scintigraphically demonstrated perfusion defects at the same times that the angiogram showed stable or even progressive obstruction. This discordant behavior of scan and angiogram is thought to reflect subsidence of postembolic vasospasm. In the 17 experimental dogs, 13 showed evidence of vasospasm, and four did not. In those that developed spasm, direct angiographic evidence of such spasm was present in all but one, manifest as diffuse constriction of small arteries and diminished parenchymal stain in vascular beds that were not directly obstructed mechanically. Although spasm diminished rapidly during the first 6 hours, there was continued and appreciable further resolution for over 48 hours in some dogs. This study reconfirms the frequent existence of vasospasm in three different embolic models, and indicates subsidence of spasm over a much longer time frame than was formerly supposed. Regression of spasm over an interval of several days suggests that perfusion scans should be performed clinically as soon as possible after a suspected embolic episode, prior to subsidence of spasm, in order to exploit the added sensitivity provided by spasm.

Thermotherapy of VX2 rabbit carcinoma. I. Augmentation by irradiation.

An induction-type radiofrequency generator was used to heat thigh implants of the VX2 rabbit carcinoma. The tumor temperature could be easily raised to over 50 degrees C, while the temperature of normal adjacent muscle generally remained at about 43 degrees C. The marked hypovascularity of the tumor, as demonstrated angiographically, probably explains this disproportionate hyperthermic reaction to administered heat. Twenty-five untreated rabbits succumbed to their tumors after a mean interval of 38 days. Of 24 rabbits with tumors heated to between 48 and 50 degrees C for 30 to 45 min, 5 (21%) were permanently cured. Of 10 rabbits treated with 1000 R in a single dose, none were cured. Of 12 rabbits treated with 1000 R, followed after 3.5 hr with 30 min of heating to 48-49 degrees C, 11 were locally cured. Thus a synergistic effect between hyperthermia and irradiation was demonstrated.

Therapeutic angiography. Its value to the surgical patient.

Standard angiographic techniques formerly used exclusively as diagnostic modalities have been modified to serve as definitive or adjunctive therapeutic measured. The techniques include transcatheter embolization; infusion of vasoactive drugs, chemotherapeutic agents and radioactive particles; tamponade of bleeding arteries and balloon catheters; extraction of vascular foreign bodies and retained biliary tract stones and transluminal arterial dilation. These techniques have been proved effective and safe when used judiciously.

Pulse-spray pharmacomechanical thrombolysis for treatment of thrombosed dialysis access grafts.

The results of pulse-spray pharmacomechanical thrombolysis (PSPMT) of 209 thrombosed hemodialysis grafts were reviewed. In PSPMT, concentrated urokinase is injected forcefully through catheters with multiple tiny sideholes or sideslits. Catheters placed in a crisscross fashion cover the entire clot simultaneously. This therapy was successful in treating patients with thrombosed grafts. Of the 200 grafts with complete therapy, 197 grafts (99%) were patent at the end of the procedure. Mean time for pulsed-spray lysis was 40 minutes. Etiologies for graft thrombosis were anastomotic venous outflow stenosis, stenosis of the venous outflow away from the anastomosis, arterial stenosis, intragraft stenosis, pseudoaneurysms, and no identifiable cause in a small percentage. There were 16 complications, 8 of which required additional therapy or potentially compromised the graft. These results suggest that pharmacomechanical thrombolysis and angioplasty provide rapid, consistent, and safe recanalization of thrombosed hemodialysis grafts and represent an additional therapeutic approach to graft management.

Accuracy of contrast-enhanced magnetic resonance angiography in chronic thromboembolic disease.

RATIONALE AND OBJECTIVES: We evaluated the accuracy of contrast-enhanced magnetic resonance (MR) angiography in demonstrating the findings of chronic pulmonary thromboembolism (CPTE) compared with conventional pulmonary angiography. METHODS: We examined 18 patients with CPTE proved by conventional pulmonary angiography and 16 healthy control patients. T1-weighted and single-breathhold, two-dimensional multiplanar spoiled gradient-recalled pulmonary images were obtained after injection of gadopentetate dimeglumine. Images were interpreted independently by two radiologists. RESULTS: All patients with CPTE were identified on MR angiography images by both readers. Sensitivity and specificity for MR angiography in diagnosing abnormal segments were 76% and 95% for reader 1 and 68% and 93% for reader 2, respectively. Sensitivity and specificity for MR angiography in depicting abnormal lobes were 83% and 96% for reader 1 and 82% and 93% for reader 2, respectively. Interobserver agreement was high; kappas for abnormal segments and abnormal lobes were .72 and .84, respectively. The T1-weighted spin-echo images demonstrated a mosaic signal intensity pattern in all patients with CPTE. CONCLUSION: Contrast-enhanced MR angiography accurately depicts abnormal segments and lobes in occlusive vascular disease and clearly distinguishes between patients with CPTE and those with healthy lungs.