Abnormal Responses of the Human Cerebral Microcirculation to Papaverin During Aneurysm Surgery

Abstract

Background and Purpose-The role of the cerebral microcirculation in delayed ischemia after subarachnoid hemorrhage remains obscure. To test the hypothesis that cerebral arterioles have a reduced capacity to dilate after subarachnoid hemorrhage, we studied the microvascular responses to papaverine (PPV) in patients undergoing aneurysm surgery. Method-In 14 patients undergoing aneurysm surgery, the diameter changes of cortical microvessels after topical application of PPV were observed using orthogonal polarizing spectral imaging. Results-In control subjects, neither arterioles nor venules showed diameter changes in response to topical PPV. In patients operated Ͻ48 hours after subarachnoid hemorrhage, PPV resulted in vasodilatation of arterioles with 45Ϯ41% increase in arteriolar diameter (Pϭ0.012). In 2 of these patients, arteriolar diameter returned below baseline value. In patients undergoing late aneurysm clipping, the diameter increase of the arterioles after PPV was 25Ϯ24% (not significant). In 2 patients of this group, no vasodilatation but focal arteriolar narrowing occurred. Conclusions-In patients with subarachnoid hemorrhage, unpredictable response patterns to PPV were observed with "rebound" vasoconstriction suggesting increased contractility of the microcirculation. Yet, diminished vasodilatory capacity of the cerebral microcirculation after subarachnoid hemorrhage was not confirmed by this study. (Stroke. 2009; 40:317-320.)

Constriction and dysfunction of pial arterioles after regional hemorrhage in the subarachnoid space

“…We observed an impaired vascular response to hypercapnia at 24 h after hemorrhage, which suggests that microcerebrovascular autoregulation is profoundly impaired after hemorrhage. Some studies have reported similar observations using papaverine in humans with SAH (Pennings et al, 2009). Next, we tested the responses to the EC-dependent vasodilator Ach and SMC-dependent vasodilator SNAP to explore the cellular events responsible for cerebrovascular dysfunction after brain hemorrhage.…”

“…Several previous studies have investigated changes in vasoreactivity after SAH (Pennings et al, 2009;Sobey et al, 1996;Sobey and Quan 1999;Vatter et al, 2007). However, most of these studies focused on the responses of basilar arteries to vasodilators after SAH (Sobey et al, 1996;Sobey and Quan, 1999;Vatter et al, 2007), which are related to the cerebral vasospasm of large arteries.…”

“…However, this type of vasospasm cannot fully account for the occurrence of DINDs, because symptoms of cerebral ischemia can occur in patients without evidence of angiographic vasospasm (vasospasm of the large conducting cerebral arteries) (Graham et al, 1983;Pennings et al, 2004). Clinical and experimental studies have indicated that cerebral microcirculatory dysfunction is involved in the pathophysiology of DINDs after SAH (Friedrich et al, 2012 et al, 1975;Pennings et al, 2009;Pennings et al, 2004;Sun et al, 2009). Because dysfunction of the cerebral microcirculation results in cerebral ischemia after SAH, leading to poor outcomes and occasionally death, detection of the underlying mechanisms is required to improve the outcomes for SAH patients.…”

Pudendal Nerve and Internal Pudendal Artery Damage May Contribute to Radiation-Induced Erectile Dysfunction

“…Papaverine is a potent vasodilator, which acts in an endothelial-independent fashion to increase cytosolic concentrations of cGMP and cAMP by way of phosphodiesterase inhibition, which leads to decreased intracellular calcium and dissociation of actin from myosin. A paradoxical response to papaverine treatment in the cerebral microvasculature has occasionally been reported in patients undergoing therapy for vasospasm (27,28). The exact mechanism underlying this altered response is unknown.…”

Direct observation during surgery shows preservation of cerebral microcirculation in patients with traumatic brain injury

“…Recently, the sidestream dark-field (SDF) system and its technical predecessor, orthogonal polarization spectral (OPS) imaging, have been introduced in the field of cerebrovascular microcirculation study. These noninvasive techniques enable the continuous observation and assessment of the small blood vessels on the cortical surface of the brain during surgery [15,[18][19][20][21].…”