Fu LW, Phan A, Longhurst JC. Myocardial ischemia-mediated excitatory reflexes: a new function for thromboxane A 2? Am J Physiol Heart Circ Physiol 295: H2530 -H2540, 2008. First published October 24, 2008 doi:10.1152/ajpheart.00790.2008.-Clinical and experimental evidence has shown that myocardial ischemia activates cardiac spinal afferents that mediate sympathoexcitatory reflex responses. During myocardial ischemia, thromboxane A 2 (TxA2) is released in large quantities by activated platelets in the coronary circulation of patients with coronary artery disease. We hypothesized that endogenous TxA 2 contributes to sympathoexcitatory reflexes during myocardial ischemia through stimulation of TxA2/prostaglandin endoperoxide (TP) receptors. Regional myocardial ischemia was induced by occlusion of a diagonal branch of left anterior descending coronary artery of anesthetized cats. Hemodynamic parameters and renal sympathetic nerve activity were recorded after sinoaortic denervation and bilateral vagotomy. Regional myocardial ischemia evoked significant increases in mean blood pressure (122 Ϯ 10 vs. 139 Ϯ 12 mmHg, before vs. ischemia), aortic flow (153 Ϯ 18 vs. 167 Ϯ 20 ml/min), first derivative of left ventricular pressure at 40-mmHg developed pressure (2,736 Ϯ 252 vs. 2,926 Ϯ 281 mmHg/s), systemic vascular resistance (0.6 Ϯ 0.1 vs. 0.9 Ϯ 0.12 peripheral resistance units), and renal sympathetic nerve activity (by 22%). The reflex nature of the excitatory responses was confirmed by observing its disappearance after blockade of cardiac nerve transmission with intrapericardial 2% procaine treatment. Moreover, application of U-46619 (2.5-10 g), a TxA2 mimetic, on the heart caused graded increases in mean arterial pressure and renal nerve activity, responses that were abolished 3 min after local blockade of cardiac neural transmission with intrapericardial procaine. BM 13,177 (30 mg/kg iv), a selective TP receptor antagonist, eliminated the reflex responses to U-46619 and significantly attenuated the excitatory responses during brief (5 min) regional myocardial ischemia. The sympathoexcitatory reflex responses to U-46619 were unchanged by blockade of histamine H 1 receptors with pyrilamine and serotonin 5-HT3 receptors with tropisetron, indicating specificity of this TP receptor agonist. These data indicate that endogenous TxA2 participates in myocardial ischemia-mediated sympathoexcitatory reflex responses through a TP receptor mechanism. sympathetic nerves; U-46619; BM 13,177 CLINICAL OBSERVATIONS INDICATE that angina pectoris can be accompanied by either hypertension and tachycardia, hypotension and bradycardia, or hypotension and tachycardia (19,20,30). The latter response very likely is mediated by the baroreceptor-induced reflex chronotropic response to the hypertension. The former two responses more likely are caused by cardiogenic reflexes. In fact, myocardial ischemia is a powerful stimulus that can activate both vagal and sympathetic (spinal) cardiac sensory nerve fibers. Excitation of cardiac vagal afferents le...

Limbal stem cells (LSCs) reside discretely at limbus surrounded by niche cells and progenitor cells. The aim of this study is to identify the heterogeneous cell populations at limbus under normal homeostasis and upon wounding using single-cell RNA sequencing in a mouse model. Two putative LSC types were identified which showed a differentiation trajectory into limbal progenitor cell (LPC) types under normal homeostasis and during wound healing. They were designated as “putative active LSCs” and “putative quiescent LSCs”, respectively, because the former type actively divided upon wounding while the later type stayed at a quiescent status upon wounding. The “putative quiescent LSCs” might contribute to a barrier function due to their characteristic markers regulating vascular and epithelial barrier and growth. Different types of LPCs at different proliferative statuses were identified in unwounded and wounded corneas with distinctive markers. Four maturation markers (Aldh3, Slurp1, Tkt, and Krt12) were screened out for corneal epithelium, which showed an increased expression along the differentiation trajectory during corneal epithelial maturation. In conclusion, our study identified two different types of putative LSCs and several types of putative LPCs under normal homeostasis and upon wounding, which will facilitate the understanding of corneal epithelial regeneration and wound healing.

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