Advances in Acute Ischemic Stroke Treatment: Current Status and Future Directions.

The management of acute ischemic stroke has undergone a paradigm shift in the past decade. This has been spearheaded by the emergence of endovascular thrombectomy, along with advances in medical therapy, imaging, and other facets of stroke care. Herein, we present an updated review of the various stroke trials that have impacted and continue to transform stroke management. It is critical for the radiologist to stay abreast of the ongoing developments to provide meaningful input and remain a useful part of the stroke team.

Pharmacokinetics of 4-aminopyridine derivatives in dogs.

Blockade of potassium channels with 4-aminopryidine (4-AP) restores conduction to demyelinated axons and improves function. Unfortunately, 4-AP causes adverse effects and its clinical effects are unpredictable and limited. Derivatives of 4-AP have been tested in models of spinal cord injury in guinea pigs; three derivatives (methyl-, ethyl- and t-butyl carbamate derivatives) showed promise. This study investigates the safety and pharmacokinetics of these derivatives in dogs. Each derivative was administered orally to dogs starting at doses below effective doses in guinea pigs, and increasing the dose on sequential days. Routine blood work was performed prior to and 24 h after drug administration, blood samples were collected at intervals over 24 h after drug administration, and dogs were monitored for side effects. Derivative plasma levels were determined using high-pressure liquid chromatography. Cerebrospinal fluid (CSF) samples were taken to determine CSF levels. No adverse effects were seen even when using doses higher than those that improved conduction in spinal cord injured guinea pigs. Peak plasma levels occurred at 36.6 (ethyl), 87 (t-butyl) and 175 (methyl) min and plasma level was related to drug dose. Penetration of the central nervous system (CNS) was good, with CSF levels higher than plasma levels for the t-butyl derivative.

Relationship between fat-to-fat-free mass ratio and decrements in leg strength after downhill running.

The purpose of this study was to determine whether greater body fat mass (FM) relative to lean mass would result in more severe muscle damage and greater decrements in leg strength after downhill running. The relationship between the FM-to-fat-free mass ratio (FM/FFM) and the strength decline resulting from downhill running (-11% grade) was investigated in 24 male runners [age 23.4 +/- 0.7 (SE) yr]. The runners were divided into two groups on the basis of FM/FFM: low fat (FM/FFM = 0.100 +/- 0.008, body mass = 68.4 +/- 1.3 kg) and normal fat (FM/FFM = 0.233 +/- 0.020, body mass = 76.5 +/- 3.3 kg, P < 0.05). Leg strength was reduced less in the low-fat (-0.7 +/- 1.3%) than in the normal-fat individuals (-10.3 +/- 1.5%) 48 h after, compared with before, downhill running (P < 0.01). Multiple linear regression analysis revealed that the decline in strength could be predicted best by FM/FFM (r2 = 0.44, P < 0.05) and FM-to-thigh lean tissue cross-sectional area ratio (r2 = 0.53, P < 0.05), with no additional variables enhancing the prediction equation. There were no differences in muscle glycogen, creatine phosphate, ATP, or total creatine 48 h after, compared with before, downhill running; however, the change in muscle glycogen after downhill running was associated with a higher FM/FFM (r = -0.56, P < 0.05). These data suggest that FM/FFM is a major determinant of losses in muscle strength after downhill running.

Effect of cocaine on left ventricular function. Relation to increased wall stress and persistence after treatment.

BACKGROUND: To determine whether alterations in left ventricular (LV) function after a cocaine infusion are due to reduced myocardial contractility or changes in loading conditions, we examined LV function in 30 morphine-sedated, closed-chest dogs. We also wanted to determine the time course of the effects of cocaine on LV function after the infusion was stopped. METHODS AND RESULTS: Two-dimensional echocardiography and hemodynamics provided LV fractional shortening and end-systolic wall stress data. Radionuclide ventriculography was also performed. Four groups of dogs received saline or cocaine infusions of 10, 30, or 100 micrograms.kg-1.min-1. Cocaine was infused for 90 minutes with ECG and arterial pressure monitoring. Animals were monitored for an additional 120 minutes after the infusion ended. Arterial pressure rose over the course of the experiment in all four groups, but saline and cocaine 10 micrograms.kg-1.min-1 did not significantly change ejection fraction. Cocaine 30 and 100 micrograms.kg-1.min-1 acutely increased arterial pressure and heart rate but decreased ejection fraction from 0.64 +/- 0.06 to 0.45 +/- 0.08 and from 0.65 +/- 0.10 to 0.46 +/- 0.11, respectively. Additionally, cocaine 100 micrograms.kg-1.min-1 decreased fractional shortening from 36 +/- 9% to 23 +/- 12%. However, cocaine 30 and 100 micrograms.kg-1.min-1 also increased wall stress from 42 +/- 15 to 65 +/- 11 g/cm2 and from 37 +/- 15 to 90 +/- 33 g/cm2, respectively. These results were analyzed by use of the relation between wall stress and fractional shortening as an index of contractility. Fractional shortening after cocaine infusion was displaced downward as a result of increased wall stress rather than changes in contractility. In addition, alteration of afterload with phenylephrine (6 micrograms/kg) and sodium nitroprusside (10 micrograms/kg) before and during infusion of cocaine 100 micrograms.kg-1.min-1 showed similar regression lines for wall stress to fractional shortening. CONCLUSIONS: Ejection-phase indexes of LV function were reduced by cocaine in this model of conscious, sedated dogs, but effects were attributable to increased wall stress rather than to reduced myocardial contractility. These effects persisted for at least 2 hours after the infusion was stopped.

Norepinephrine-induced left ventricular dysfunction in anesthetized and conscious, sedated dogs.

These studies were conducted to evaluate effects of high dose norepinephrine infusion on left ventricular function in anesthetized and conscious dogs. Separate groups of pentobarbital anesthetized closed-chest dogs received norepinephrine infusion for 90 min followed by 1 h of recovery. Arterial pressure, electrocardiogram, two-dimensional echocardiogram and an equilibrium radionuclide angiogram were monitored. One hour following infusion of norepinephrine, left ventricular ejection fraction was reduced in a dose-dependent fashion. Fractional shortening was similarly reduced, with increased left ventricular systolic and diastolic dimensions also observed. Left ventricular end-systolic wall stress was increased at 60 min following infusion of norepinephrine but not saline: saline, 68 +/- 8, norepinephrine, 4 micrograms/kg/min, 113 +/- 8 g/cm2. The left ventricular end-systolic wall stress/fractional shortening relationship showed reduction of contractility. In 10 conscious dogs pretreated with morphine, norepinephrine at 5 micrograms/kg/min x 90 min produced similar changes to those seen in anesthetized animals. Ejection fraction was reduced from 0.69 +/- 0.3 to 0.36 +/- 0.04 at 60 min post infusion. Fractional shortening was also reduced. Left ventricular end-diastolic dimension was increased. However, when animals were followed for 1 week, complete recovery occurred within 48 h. Histology showed mild contraction band necrosis in acute experiments and mild perivascular fibrosis in chronic experiments. Therefore, norepinephrine cardiotoxicity produced significant left ventricular dilation and reduction of ejection phase indices of left ventricular function associated with reduced contractility. In chronic dogs, histologic changes were mild, and left ventricular dysfunction was reversible.

Effect of chronic native flow competition on internal thoracic artery grafts.

Residual competitive flow from the native coronary artery has been proposed as a mechanism that reduces flow in an internal thoracic artery graft (ITA), resulting in narrowing and ultimately failure of the graft. Results from acute experiments have indicated that competitive flow from a fully patent native artery did not abolish ITA graft flow. The present study was designed to examine the consequences of dynamic flow competition between the native vessel and the ITA graft in a chronic model. Fifteen mongrel dogs underwent coronary artery bypass grafting using the pedicled left ITA anastomosed to the normal, fully patent circumflex (CFX) coronary artery. The procedure was performed through a sterile thoracotomy, without systemic cardiopulmonary bypass, using a brief local occlusion to construct the anastomosis. Intraoperatively, ITA flow was measured in situ on the chest wall, before the pedicle was mobilized. Internal thoracic artery graft and distal CFX flow were measured after the anastomosis was completed, with and without brief occlusion of the proximal CFX. Angiography was performed 72 hours, 4 weeks, and 8 weeks later; graft patency and diameter were evaluated. After 8 weeks, open-chest direct flow measurements comparable with the intraoperative assessment were obtained. Two grafts (13%) occluded early, the technical result of poor anastomotic construction. In the 13 remaining animals, all grafts were widely patent at all time points. Internal thoracic artery flow in situ averaged 10.9 +/- 7.8 mL/min (mean +/- standard deviation), and was maintained after grafting (11.5 +/- 4.4 mL/min; p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Unusual cutaneous adverse reaction to warfarin therapy.

We have described a patient who had an extensive maculopapular pruritic rash after a single dose of warfarin. Although dermatologic reactions have been reported with this drug, the pathogenesis of these reactions remains unknown.

Deep venous thrombosis and pulmonary embolism following cardiac catheterization.

We report 4 cases of deep venous thrombosis and/or pulmonary embolism after diagnostic cardiac catheterization. Two of these cases followed left heart catheterization alone.

A radioimaging technique for quantifying regional myocardial blood flow.

We developed a radioimaging technique for measuring regional myocardial blood flow (rMBF) in 5 mm2 myocardial tissue using canine closed-chest models. RMBF was measured in three groups: (1) total occlusion of left anterior descending (LAD) coronary artery with microfibrillar collagen, (2) fixed stenosis of LAD with angioplasty balloon, and (3) comparison of clinical dose response of adenosine (AD) and dipyridamole (DP) on rMBF. In these studies, rMBF in every 5 mm2 tissue was measured throughout the epicardium and endocardium. In groups 1 and 2, rMBF was also measured during adenosine-induced coronary hyperemia (ADICH). In group 1 (n = 7), rMBF measured at 6 hours post-LAD occlusion in epicardial infarct center (IC), peri-infarct (PI) and normal zone (NZ) were 17 +/- 7, 55 +/- 8, and 132 +/- 12 ml/min/100 tissue, respectively. The area and location of infarct seen in TTC staining matched with rMBF images. During ADICH, the corresponding rMBF were 16.2 +/- 13.9, 98.3 +/- 53.0, and 226.0 +/- 103.6 ml/min/100 g tissue, respectively. RMBF measured during ADICH in group 2 (n = 4) in areas of LAD stenosis (LS), surrounding stenosis (SS), and no stenosis (NS) were 120 +/- 58, 249 +/- 123, and 432 +/- 181 ml/min/100 gm tissue, respectively. In group 3, rMBF measured during 3 min into 0.14 mg/kg/min adenosine infusion in areas perfused by LAD, circumflex (CX) and right coronary artery (RCA) were 244 +/- 22, 238 +/- 19, and 215 +/- 19 ml/min/100 g tissue, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Competitive flow from a fully patent coronary artery does not limit acute mammary graft flow.

The shriveled, stenotic mammary graft sometimes observed after internal mammary artery (IMA) to coronary artery bypass grafting has been attributed to competitive flow from the insufficiently stenosed native coronary vessel. To study further the effects of native coronary artery competing flow on IMA graft flow, 10 dogs (mean weight, 23.5 +/- 3.69 kg) underwent coronary artery bypass grafting using the pedicled left IMA anastomosed to a normal, fully patent proximal circumflex (CFX) coronary artery. The procedure was performed through a left thoracotomy, off pump, using a brief local occlusion to perform the anastomosis. Native in situ IMA flow, CFX flow distal to the anastomosis, and IMA graft flow were measured using calibrated electromagnetic flow probes. When the CFX proximal to the anastomosis was occluded transiently, IMA flow increased to supply 100% of the previously measured distal CFX flow (60.2 +/- 7.9 mL/min). When both the IMA graft and CFX proximal to the anastomosis were patent, total distal perfusion was maintained (58.9 +/- 7.8 mL/min) and relative IMA graft flow (26.5 +/- 3.3 mL/min) was proportional to the relative diameter of the IMA graft to the native coronary artery (r = 0.96). The mean flow in the IMA in situ on the chest wall before its division was 23.8 +/- 8.1 mL/min. These results suggest that, at least acutely in a canine model, IMA graft flow is maintained above in situ levels even when grafted to a completely patent coronary artery and that acute competitive flow probably does not cause mammary artery shriveling.

Omentoplasty or tube drainage for the management of the residual cavity following the removal of an hepatic hydatid cyst.

We have reviewed a series of 124 consecutive cases of hepatic hydatid cysts in 102 patients treated surgically in Benghazi, Libya, over a period of five years. Overall mortality was 3.9%. The rate of post-operative complications was 37.5%. Cysts already complicated with infection, intrabiliary communication or intra-peritoneal rupture accounted for 30.6% of the cases. They were all treated by means of removing the endocyst and external tube drainage of the residual cavity. In this subgroup, the post-operative complications' rate was 89%. In the 74 uncomplicated cysts, removal of the parasite was followed by omentoplasty in 25 cases and external tube drainage in 49 cases. Postoperative complications occurred in 16% of the omentoplasty group and 8.2% of the drainage group. It is concluded that omentoplasty for the obliteration of the residual cavity may be used in uninfected and relatively inaccessible cysts. In the majority of cases, however, external tube drainage retains its value as a simple and safe procedure.

Cardioprotective effects of captopril in myocardial ischaemia, ischaemia/reperfusion and infarction.

Several experimental studies have suggested that the sulphydryl-containing angiotensin-converting enzyme inhibitor, captopril, has cardioprotective effects in the setting of acute myocardial ischaemia, ischaemia/reperfusion and infarction. We have observed that captopril can reduce the degree of dilatation and early functional myocardial infarct expansion produced by 3 h of permanent coronary artery occlusion in anaesthetized, open-chest dogs. In addition, captopril has been shown to limit experimental infarct size, reduce the incidence of reperfusion arrhythmias, and improve contractile function of stunned myocardium. When administered chronically after myocardial infarction, both experimental and clinical evidence suggests that captopril reduces left ventricular dilatation. Captopril is currently being tested in large clinical trials as adjuvant therapy to thrombolysis.

Severe bradycardia following electrical cardioversion for atrial tachyarrhythmias in patients with acute myocardial infarction.

Bradycardia following electrical cardioversion is an uncommon complication. The present report describes three patients who developed life-threatening bradycardia following electrical cardioversion for atrial tachyarrhythmias in the setting of an acute myocardial infarction. All three patients had multivessel coronary artery disease with a totally occluded right coronary artery and a possibility of ischemic sinus node dysfunction. When electrical cardioversion is undertaken for new onset of atrial tachyarrhythmia in the setting of an acute myocardial infarction, measures for immediate, temporary pacing should be easily available.

Reassessment of the association between gastrointestinal arteriovenous malformations and aortic stenosis.

PURPOSE AND PATIENTS AND METHODS: The purported association between aortic stenosis and gastrointestinal arteriovenous malformations (AVMs) has not been rigorously evaluated. The diagnosis of aortic stenosis in most the prior studies has been based on clinical examination. We therefore utilized two-dimensional and Doppler echocardiography to document the presence or absence of aortic stenosis in 29 men with gastrointestinal AVMs documented by endoscopy. RESULTS: Of the 29 patients studied, 22 (76 percent) had ejection systolic murmurs and 18 (62 percent) had echocardiographic evidence of aortic sclerosis. However, none of the patients had any evidence of aortic stenosis as assessed by Doppler echocardiography. CONCLUSION: Although previous case reports and retrospective studies have suggested an association between gastrointestinal AVMs and aortic stenosis, our study does not support this association and suggests the need for a prospective trial.

Functional infarct expansion, left ventricular dilation and isovolumic relaxation time after coronary occlusion: a two-dimensional echocardiographic study.

Left ventricular dilation and infarct expansion after acute myocardial infarction are associated with an increased morbidity and mortality. The purpose of this study was to determine whether angiotensin-converting enzyme inhibition could reverse left ventricular dilation and improve the diastolic properties of the left ventricle very early after coronary occlusion. The acute time course of left ventricular dilation and infarct expansion (as determined by two-dimensional echocardiography) and early diastolic isovolumic relaxation time were studied in 20 dogs subjected to 3 h of coronary occlusion. End-diastolic area before occlusion was 8.4 +/- 0.5 and 8.9 +/- 0.7 cm2 (p = NS) in the captopril- and the saline-treated group, respectively. At 30 min after occlusion (pretreatment), end-diastolic area increased to 12.6 +/- 0.8 cm2 in the captopril-treated group (p less than 0.01) and 11.3 +/- 0.9 cm2 (p less than 0.05) in the saline-treated group. Three hours after occlusion and after captopril treatment, end-diastolic area decreased to 9.4 +/- 0.6 cm2 (p less than 0.05 versus 30 min after occlusion), whereas it was unchanged in the saline-treated group. Functional infarct expansion (as assessed by end-systolic anterior to posterior endocardial segment length ratio) occurred early after occlusion, and captopril reduced this expansion. Pretreatment values for early diastolic isovolumic relaxation time increased from 29.1 +/- 2.4 to 50.5 +/- 2.9 ms in captopril-treated dogs (p less than 0.01) and from 34.3 +/- 3.4 to 46.9 +/- 2.7 ms in saline-treated dogs (p less than 0.01) after coronary occlusion, implying a worsening of diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of acid base disturbance, septic shock, and calcium and phosphorous abnormalities on cardiovascular function.

Systemic acidosis has a negative inotropic effect on myocardial function, which in the intact animal, is counteracted by the activation of the sympathoadrenal system. Although there are extensive animal data in this field, human studies quantifying the influence of systemic acidosis on myocardial function in various disease states is lacking. In patients with hypocalcemia, a single infusion of calcium does not sustain increased calcium levels, and the hemodynamic improvement is only transient. Hemodynamic changes in septic shock are complex, and there are convincing data documenting myocardial dysfunction in sepsis. There is a need for elucidating the biochemical characteristics of the myocardial depressant factor (or factors).

The cardiotonic agent amrinone does not increase anatomic infarct size.

The effect of the positive inotropic agent amrinone on anatomic infarct size induced by coronary artery occlusion and reperfusion in dogs is unknown, although previous studies have shown that amrinone increases indices of myocardial ischemia during very brief coronary artery occlusions. Thus, this study was performed to determine if amrinone changes anatomic infarct size and improves hemodynamics induced by 3 h of coronary occlusion and 3 h of reperfusion in anesthetized, open-chest dogs. Amrinone (1-mg/kg bolus followed by 6 mg/kg/h) or an equivalent volume of saline was administered intravenously for 3 h beginning 30 min postocclusion. The area at risk was 19.7 +/- 2.6% in the control group (n = 9) and 20.2 +/- 1.8% in the amrinone-treated group (n = 9; p = NS). The amount of the area at risk that developed infarction was 60.6 +/- 6.1% in the control group and 54.6 +/- 5.6% in the amrinone-treated group (p = NS). Pretreatment left ventricular end-diastolic pressure increased from 11.4 +/- 1.8 to 20.1 +/- 3.0 mm Hg (p less than 0.05) in the control group and from 10.8 +/- 1.3 to 17.3 +/- 1.3 mm Hg (p less than 0.05) in the amrinone-treated group following coronary artery occlusion. During coronary occlusion, amrinone administration significantly increased left ventricular maximum +dP/dt [+483 +/- 85 vs. -11 +/- 53 mm Hg/s (p less than 0.01) in amrinone vs. control group, respectively] and heart rate (+27 +/- 6 vs. -4 +/- 2 beats/min; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)