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Biomedical subjects

S M Oppenheimer

Publications and source records attributed to S M Oppenheimer.

At least 19 recordsLinked to original sources

Left insular stroke is associated with adverse cardiac outcome.

BACKGROUND: After stroke, 10% of patients have adverse cardiac outcomes. Left insular damage may contribute to this by impairing sympathovagal balance (associated with cardiac structural damage and arrhythmias). METHODS: The authors conducted a prospective study of 32 patients with left insular stroke (Group 1) and 84 patients with non-insular stroke/TIA (Group 2). Adverse cardiac outcomes (cardiac death, myocardial infarction, angina, and heart failure) were assessed over 1 year. Myocardial wall motion was investigated with transesophageal echocardiography. RESULTS: Group 1's cardiac outcome relative risk (RR) compared with Group 2 was 1.75 (95% CI: 1.02, 3.00, p = 0.05). Left insular stroke remained an independent predictor of cardiac outcome in multivariate analyses. Sensitivity analysis excluding TIA and angina showed similar results. For Group 1 patients without symptomatic coronary artery disease (SCAD), cardiac outcome RR = 4.06 (95% CI: 1.83, 9.01, p = 0.002). For Group 1 with SCAD, RR = 0.36 (95% CI: 0.06, 2.13, p = 0.14). Cardiac wall motion impairment was also associated with left insular stroke independent of CAD or nonischemic heart disease. Right insular stroke was not associated with adverse cardiac outcomes or cardiac wall motion impairment. CONCLUSIONS: Left insular stroke is associated with an increased risk of adverse cardiac outcome and decreased cardiac wall motion compared to stroke in other locations and TIA. This was particularly marked in patients without symptomatic coronary artery disease (SCAD). In patients with SCAD, the cardioprotective effect of medications, especially beta-blockers alone or combined with ischemic preconditioning, may explain the lack of association in this subgroup.

Brain↗

Risk factors for intracardiac thrombus in patients with recent ischaemic cerebrovascular events.

BACKGROUND: Intracardiac thrombus is a common cause of cardiogenic cerebral ischaemia. Stroke recurrence is high, but thrombus detection with therapeutic intervention can reduce the risk. Accurate detection requires transoesophageal echocardiography (TOE), which is semi-invasive and costly. OBJECTIVE: To identify risk factors for cardiac thrombus, enabling selection of patients for TOE and initiation of measures to prevent the formation of cardiac thrombus. METHODS: 151 consecutive patients with ischaemic stroke or transient ischaemic attacks (mean age 62 years) underwent TOE for intracardiac thrombus detection within one week of a qualifying event. RESULTS: Intracardiac thrombus was found in 26% of the patients (70% in the left atrial appendage). Multivariate analysis indicated the following clinical correlates: large stroke, odds ratio (OR) = 2.8 (95% confidence interval, 1.2 to 6.4); symptomatic coronary artery disease, OR = 3.0 (1.2 to 7.4); and ECG evidence of ischaemia, OR = 2.8 (1.1 to 7.7). Neither carotid stenosis >70%, nor stroke location correlated with the presence of thrombus. CONCLUSIONS: Clinical factors correlate with and appear to be risk factors for cardiac thrombus in patients with recent cerebral ischaemia. These may be used to select appropriate patients for invasive and costly TOE investigation, irrespective of the presence of significant carotid stenosis (>/=70%) or stroke location.

Aged↗

Effect of adenosine on cerebral blood flow velocity.

BACKGROUND AND PURPOSE: Evidence suggests that adenosine (ADN) is a potent vasodilator of cerebral vessels. However, the feasibility of manipulating human cerebral vascular resistance with ADN has not been assessed by means of TCD. The purpose of this study was to quantitatively estimate the change in middle cerebral artery cerebral blood flow velocity (CBFV) in response to intravenous ADN infusion in humans. METHODS: Eleven patients with subacute cerebrovascular events (ischemic stroke, transient ischemic attack, or hemorrhage) undergoing adenosine-thallium stress testing were studied before, during, and after ADN infusion to evaluate the effect of ADN on cerebral blood flow velocity. Continuous blood pressure (BP), heart rate (HR), respiration rate (RR), end-tidal CO2 (ET-CO2), and transcranial Doppler ultrasonography monitoring of CBFV and pulsatility index (PI) in both middle cerebral arteries were performed. RESULTS: The mean CBFVs were 65.4 +/- 19.2 cm/s before, 55.4 +/- 18.1 cm/s during, and 64.1 +/- 22.5 cm/s after ADN infusion, which represents a statistically significant decrease during ADN test compared with both baseline (P = .007) and posttest levels (P = .017). The PI was increased during the test (0.91 +/- 0.2) when compared with baseline (0.71 +/- 0.1) (P = .007). During ADN injection, mean HR increased (P = .004) and mean ET-CO2 levels decreased significantly (P = .003). Mean BP and RR did not change significantly. CONCLUSIONS: The authors hypothesize that any direct vasodilatory effect of ADN on the distal cerebral peripheral vasculature may be negated by an effect of ADN on depth of respiration resulting in hypocapnia and secondary distal vasoconstriction.

Adenosine↗

Electrophysiological evidence for reciprocal insulo-insular connectivity of baroreceptor-related neurons.

The recent indications of specialized lateralization of cardiovascular regulation within the right and left posterior insular cortex of the rat, suggest the possibility of transcallosal connectivity between these regions. This has not been previously demonstrated using physiological techniques. Extracellular neural recordings in 34 urethane anesthetized male Sprague-Dawley rats demonstrated reciprocal interinsular antidromic and orthodromic activation, elicited with similar median onset latencies (18 ms). The corresponding conduction velocity of these fibers (0.6 m/s) suggests that they may be unmyelinated. Many of the cells showing interhemispheric connectivity also responded to baroreceptor activation, further emphasizing the connectivity pattern in baroreceptor-related units. Both 1 and 25 Hz microstimulation of the contralateral insula indicated that the most frequent orthodromic response was inhibitory, either alone or as part of a biphasic pattern including activation. Chemical stimulation of the insula using L-glutamate was associated with both excitatory and inhibitory orthodromic activation of the contralateral posterior insula, confirming that the orthodromic electrical stimulation was not solely due to activation of fibers of passage. These data suggest that the two insulae may communicate with each other to integrate and balance cardiovascular function between hemispheres.

Action Potentials↗

Baroreceptive and somatosensory convergent thalamic neurons project to the posterior insular cortex in the rat.

Connectivity between the rat posterior insula and the ventrobasal thalamus has been demonstrated anatomically. Neurons convergent for baroreceptor and nociceptive input have also been identified in the homologous anterior insula of the primate. Whether similar convergent cells exist in the ventrobasal thalamus was investigated in 30 urethane anesthetized male Sprague--Dawley rats. Six classes of cells were identified in the right ventrobasal thalamus: (a) 83/159 (52%) baroreceptive and nociceptive convergent units; (b) 2/159 (1%) convergent cells responding to baroreceptor activation and light touch; (c) 44/159 (28%) purely nociceptive units; (d)10/159 (6%) purely baroreceptive units; (e) 1/159 (0.6%) cells responding to brush alone and (f) 19/159 (12%) unresponsive units. Of the viscerosomatic convergent cells, 66/85 (78%) were situated in the ventroposterolateral nucleus (VPL), 6/85 (7%) in the ventroposterolateral parvicellular nucleus (VPLpc), and 13/85 (15%) in the ventroposteromedial nucleus (VPM). Fifteen right ventrobasal thalamic units were antidromically activated and 34 units orthodromically activated by right posterior insular microstimulation. Cobalt injection into the right ventrobasal thalamus blocked the right insular response to baroreceptor activation by >70%. These data indicate: (a) baroreceptive and somatosensory nociceptive convergent units exist in the ventrobasal thalamus; (b) thalamic convergent neurons project directly to the ipsilateral posterior insula and receive reciprocal insulothalamic projections; and (c) a significant proportion of baroreceptor input relays to the posterior insula through the ipsilateral ventrobasal thalamus.

Animals↗

Neurogenic ST depression in stroke.

BACKGROUND: Stroke is occasionally associated with ECG repolarization changes including ST depression. Recent evidence suggests a neurogenic contribution to these abnormalities in stroke patients. Animal studies implicate the insular cortex in cardiovascular control. We describe a patient with a left insular infarct and without cardiac or coronary artery disease, who developed ST depression indicating a neurogenic etiology. CASE DESCRIPTION: A 48 year-old female, with no risk factors for stroke, developed sudden expressive aphasia. MRI brain showed an infarct in the left insular cortex. Twenty-four hour Holter monitoring on the third day revealed transient ST depression more than 1.5 mm, which was not reproducible on subsequent monitoring. Transesophageal echo-cardiography (TEE) was normal. She had no cardiac symptoms and serial ECGs, cardiac enzymes (CKMB) and adenosine thallium scan were normal. To-date, there had been no cardiac events like congestive heart failure or myocardial ischemia. CONCLUSION: These findings suggest neurogenic ST depression is related to the left insular infarct in view of the normal adenosine thallium scan, non-reproducibility and evanescence of the ST segment changes and lack of associated cardiac symptoms. When neurogenic ST depression is combined with underlying coronary artery disease, it may adversely influence cardiac outcome after stroke.

Cerebral Cortex↗

Monkey insular cortex neurons respond to baroreceptive and somatosensory convergent inputs.

To investigate possible convergence of autonomic and somatosensory input in the insula of the non-human primate, extracellular single-unit recordings were obtained from 81 neurons (43 insular and 38 in surrounding cortex) during application of cutaneous nociceptive stimuli (pinch) and baroreceptor challenge in six anesthetized monkeys (Macaca fascicularis). All cells were also tested with light touch (brush) stimulation. Twenty-six units responded to blood pressure changes; 20 (80%) were identified within the insula (P < 0.001). The majority of these insular units (16/20) also responded to nociceptive pinch (convergent units). More units responsive to changes in blood pressure (unimodal and convergent) were found in the right (18/29, 62%) than in the left insular cortex (2/14, 14%)(P = 0.004). Twenty-nine insular neurons responded to nociceptive stimuli; 16 of these were convergent units and 13 showed unimodal responses to somatosensory stimuli alone. These cells had wide bilateral receptive fields including face, hand, foot and tail. Ten insular neurons were unresponsive to both sets of stimuli (non-responsive cells); significantly more of these cells (28/38) were identified in extrainsular locations (P < 0.01). We suggest that the primate insular cortex may be involved in the integration of cardiovascular function with somatosensory (principally nociceptive) input. This view supports the emerging role of the insular cortex as an important forebrain site of viscerosomatosensory regulation with clinical implications for cardiovascular regulation under conditions of stress and arousal.

Animals↗

TCD, MRA and MRI in acute cerebral ischemia.

OBJECTIVES: The aim of this study was to determine accuracy of transcranial Doppler ultrasound (TCD) and compare efficacy of three non-invasive tests [TCD, magnetic resonance angiography (MRA), and magnetic resonance imaging (MRI)] in patients with acute cerebral ischemia. MATERIAL AND METHODS: This prospective study involved 30 patients. MRI, MRA, and TCD were performed within 24 h after onset of ictus. The 2nd MRI was repeated at 48-72 h and was used as the standard for the evaluation of sensitivity and specificity of MRA, TCD, and initial MRI. RESULTS: TCD showed a sensitivity of 96% and a specificity of 33% for recognizing abnormal cerebral blood flow velocities. MRA showed a sensitivity of 46% and a specificity of 75% for assessing intracranial vascular anatomy, while initial MRI revealed a sensitivity of 84% and a specificity of 100% for evaluation of ischemic parenchymal changes. CONCLUSION: Our results revealed that TCD is an accurate indicator of blood flow status and correlated well with MRI, MRA abnormalities in acute stroke.

Adult↗

Insular cortex lesions alter baroreceptor sensitivity in the urethane-anesthetized rat.

Cardiovascular representation has been demonstrated within the insular cortex and lateralization has been previously inferred. In this study, baroreceptor gain was investigated in response to the systemic injection of the pressor agent phenylephrine (PE) and the depressor agent sodium nitroprusside (SNP) in 57 urethane-anesthetized, male Sprague-Dawley rats before and after single lesion placement. Lesions mainly confined to the anterior insula (left or right) or the adjacent cortex were without significant effect on baroreceptor gain. Left posterior insular lesions, however, significantly increased baroreceptor gain (p<0.0001) whereas right posterior insular lesions had no effect on baroreceptor gain although heart rate and blood pressure were both significantly increased after lesion placement (p<0.05). These data suggest that: (1) the posterior insula (and not surrounding cortex or anterior insula) is primarily involved in cardiovascular control; (2) the left insular cortex may be chiefly concerned with parasympathetic cardiac regulation. Conversely, the right posterior insular cortex may regulate both cardiac and vasomotor sympathetic tone, as has been suggested in other species.

Anesthetics, Intravenous↗

Characterization of baroreceptor-related neurons in the monkey insular cortex.

Insular neurons responsive to baroreceptor challenge have been identified in the rat, but not previously in primates. Characterization of baroreceptor-related neurons was performed in 15 anesthetized monkeys (Macaca fascicularis) using extracellular single-unit recording techniques. 131 units were investigated within the insula and surrounding regions. Based on their responses to phenylephrine hydrochloride (PE) and sodium nitroprusside (SNP), three types of units were distinguished: 35/131 (27%) sympathoexcitatory (SE), 12/131 (9%) sympathoinhibitory (SI) and 84 (64%) null units. More baroreceptive units were found within the insula (38/73, 52%) than in surrounding areas (9/58, 16%) (p < 0.001). Lateralization was indicated with more baroreceptive units being encountered within the right insula (28/44, 64%) than the left (10/29, 34%) (p = 0.02). The majority of the responsive units were located within the dysgranular and granular insula in layers II, III and V/VI. These data suggest that cardiovascular representation may occur in the primate insula as has been shown in other species.

Animals↗

Usefulness of transesophageal echocardiography in predicting mortality and morbidity in stroke patients without clinically known cardiac sources of embolus.

This study tested the hypothesis that stroke patients without a cardiac source of embolism suspected by clinical examination can be risk stratified by transesophageal echocardiography. Forty ischemic stroke patients without atrial fibrillation, prosthetic valves, ejection fraction < 20%, or recent myocardial infarction underwent multiplane transesophageal echocardiography: 24 (designated high risk) had > or = 1 of the following: left heart thrombus, vegetation, mass or spontaneous echo contrast, mobile ascending aortic or arch debris, patent foramen ovale, atrial septal defect or aneurysm, mitral annular calcification, mitral valve thickening, prolapse or mitral valve strands. End points were death, recurrent stroke, transient ischemic attack, myocardial infarction or peripheral embolism. Thirty-eight patients (95%) (23 high, 15 low risk) were followed for 14 +/- 8 months: 9 (24%) died of vascular causes including 4 who had a cardiac cause of death and 5 who had fatal strokes. Eight had recurrent strokes (4 nonfatal) and 1 nonfatal myocardial infarction occurred. Cardiovascular survival was predicted by transesophageal echocardiography: survival rates were 92% (low risk) and 63% (high risk) at 24 months (p = 0.036). Left atrial enlargement was independently associated with death from stroke (fatal stroke occurred in 25% of those with atrial enlargement compared to 8% of those with normal atrial dimension, p < or = 0.03), as was left atrial spontaneous echo contrast (50% died vs 9% without contrast, p < or = 0.03). Left ventricular hypertrophy and aortic atherosclerosis were both associated with the risk of recurrent stroke (30% of patients with ventricular hypertrophy had recurrent stroke compared to 10% with normal wall thickness (p < or = 0.05); 30% with aortic atherosclerosis had a recurrent stroke compared to none with a normal aorta (p < or = 0.05). Thus, transesophageal echocardiography clearly identifies patients at a high risk for cardiovascular mortality and morbidity after stroke despite an unsuspected source of embolism by clinical examination.

Aged↗

Distribution of cardiovascular related cells within the human thalamus.

Representation of cardiovascular function has not been investigated in the human thalamus. In the rat, the insular cortex is the principal forebrain site of cardiovascular representation whose afferents originate from a circumscribed thalamic area (nucleus ventralis posterolateralis-parvicellular portion, VPLpc). We therefore evaluated 4481 thalamic cells for phasic cardiovascular activity using extracellular recording techniques in 60 unanesthetized patients undergoing neurosurgical procedures. We identified 26 cells with phasic activity strongly related to the cardiac cycle in 10 patients. These cells clustered within the ventrocaudal nucleus of the thalamus (the principal sensory nucleus analogous to the ventral posterior thalamic group in the rat and monkey) and were equally distributed between the right and left sides. The majority of these cells (17/26) showed peaks of phasic neuronal activity within 50 ms of the peak systolic pressure; 35% had peripheral cutaneous fields in areas to which cardiac pain is often referred. We suggest that these cells may be involved in the integration of afferent baroreceptor information; may possibly be concerned with the generation and/or processing of central cardiac pain in humans; and that their derangement may possibly contribute to the lethal cardiovascular disturbances which occur in fatal familial insomnia.

Action Potentials↗

Cardiac disorders and stroke.

Cardiac disorders are increasingly recognised as an important source of cerebral embolism. Atrial fibrillation is the most common cardiac dysrrhythmia that can predispose to stroke. Recent advances have significantly increased the identification of clinical, hematological and echocardiographic risk factors that predict the occurrence of atrial fibrillation related stroke. Also, clinical risk stratification has been used to determine medical therapy (aspirin or warfarin) for prevention of atrial fibrillation related brain embolization. Among the various structural heart diseases causing stroke, the role of patent foramen ovale remains controversial. Strides have been made in the use of ultrasonographic techniques such as transesophageal echocardiography and contrast transcranial doppler to detect patent foramen ovale. Coronary artery bypass grafting is often performed in patients with concomitant aortic atheroma and carotid stenosis that may predispose to stroke in the perioperative period. It is now possible to identify perioperatively significant aortic atherosclerosis (using transesophageal echocardiography and aortic ultrasound) and significant carotid disease (using carotid ultrasound) and make appropriate modifications in surgical technique to reduce the incidence of coronary artery bypass grafting related stroke. Because of shared risk factors it is not surprising that coronary artery disease is frequently found in stroke patients. Recent studies suggest that more than one-third of stroke patients have asymptomatic coronary artery disease. Conversely, the brain damaged by infarction may itself be responsible for the production of cardiac structural and electrical abnormalities. Both these factors may contribute to the finding that cardiac events are the leading cause of death in stroke patients on long term follow-up. Recognition of these correlations has enhanced our ability to treat and prevent stroke related mortality.

Animals↗

Characterization, distribution and lateralization of baroreceptor-related neurons in the rat insular cortex.

The insular cortex contains a site of cardiovascular representation. Stimulation experiments suggest a discrete localization within the rostral posterior insula. In 34 urethane-anesthetized male Sprague-Dawley rats, we investigated whether cells responsive to baroreceptor stimulation with phenylephrine and sodium nitroprusside were selectively clustered within the insula compared with the surrounding frontoparietal cortex, the extent of distribution of these responsive cells within the insula, and whether there was any lateralization of response. In addition, we characterized the cells as SE (sympathoexcitatory), SI (sympathoinhibitory) or null cells using the criteria of Barman. Of the 128 insular cells investigated with extracellular recording techniques, 70% responded to baroreceptor manipulations compared to 32% of the 57 cells investigated outside the insula (P < 0.0001). The majority of the responsive cells were SE units and were distributed widely throughout the insular cortex including anterior areas not previously thought to be involved in cardiovascular control. Within the rostral posterior insula from which cardiovascular effects are mainly obtained in stimulation experiments, lateralization was identified, with significantly more cells responding to blood pressure changes being found within the right posterior insula than the left (P < 0.003). These data confirm the importance of the right posterior insula in the rat as a site of cardiovascular representation; identify a more extensive distribution of cells responsive to blood pressure changes within the insula than previous studies and imply more widespread convergence of visceral afferent information within the insula.

Animals↗

MR angiography in acute cerebral ischemia of the anterior circulation: a preliminary report.

PURPOSE: To determine the prevalence of major vessel occlusion in cases of acute cerebral ischemia of the anterior circulation by using MR angiography and to assess the frequency of spontaneous thrombolysis. METHODS: Thirty patients with an initial clinical diagnosis of possible acute stroke of the anterior circulation made within 24 hours of the event were studied with conventional T2-weighted MR imaging and with two-dimensional and three-dimensional time-of-flight MR angiography. Studies were repeated if the initial study showed partial or complete occlusion. RESULTS: Of the 30 patients studied six (20%) had a final diagnosis of a transient ischemic attack and 24 (80%) had a stroke of the anterior circulation as confirmed by T2 abnormalities and persistence of clinical symptoms. Twelve (50%) of the stroke patients had a major vessel abnormality, either partial or complete occlusion, at MR angiography. Of these 12 patients, nine subsequently had follow-up MR angiography, and only two of these had a change in the findings. One patient with diminished flow signal had progression of the occlusion and another patient had flow signal in a vessel where no flow was seen initially. CONCLUSION: MR angiography can show patients with acute cerebral ischemia and major vascular occlusive disease. Of those with partial or complete occlusion, progression of thrombus or spontaneous recanalization occurs infrequently.

Acute Disease↗