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Biomedical subjects

K S Murthy

Publications and source records attributed to K S Murthy.

At least 37 records · Page 2Linked to original sources
PubMed1999

Median sternotomy single stage complete unifocalization for pulmonary atresia, major aorto-pulmonary collateral arteries and VSD-early experience.

OBJECTIVE: It is a prospective study to assess the results of median sternotomy, single stage complete unifocalization and repair for ventricular septal defect (VSD), pulmonary atresia and major aorto pulmonary collateral arteries (MAPCAs). METHODS: From June 97 to August 98, 20 patients were treated with single stage complete unifocalization and repair. Their ages ranged from 6 months to 11 years. Through median sternotomy, all MAPCAs were dissected and looped. On cardiopulmonary bypass, MAPCAs were anastomosed to native pulmonary arteries (PAs) or to MAPCAs. VSD was closed if possible and RV to PA continuity was established with a homograft conduit. If complete repair was not suitable, central shunt was done from ascending aorta to reconstructed PA with a polytetrafluroethylene graft. The patients were divided into three groups according to the arborization pattern in the lungs. Group 1 had well formed native PAs with MAPCAs, group 2 had hypoplastic PAs with MAPCAs and group 3 had only MAPCAs. RESULTS: Twenty patients had 21 procedures. All MAPCAs were unifocalized with tissue-to-tissue anastomosis for future growth, except one in whom polytetrafluroethylene tube graft was used to attain the confluence. In group 1, all seven patients had complete unifocalization and repair. In group 2, four patients had RV to PA conduit and two patients had central shunt. In group 3, three patients had complete repair, three patients had RV to PA conduit and one patient had central shunt. There were three deaths, two in group 2 and one in group 3. The first patient died due to a wrong decision to close the VSD, the second patient died due to missed large MAPCA in preoperative angio and the third patient was a 7-year-old boy who died with irreversible pulmonary vascular changes due to unprotected MAPCAs. CONCLUSIONS: To conclude, complete repair/RV-PA conduit/central shunt should be done according to the size of the total pulmonary vasculature in patients with group 1, 2 and 3 with protected PAs/MAPCAs and in hypoplastic or absent PAs with unprotected MAPCAs (less than 1 year) and protected MAPCAs. We are yet to determine the surgical procedure to be performed in hypoplastic/absent PAs with unprotected MAPCAs more than 1 year. It is very essential to delineate all the MAPCAs up to the level of the diaphragm preoperatively.

Cardiac Surgical Procedures↗
PubMed1998

Differential regulation of phospholipase A2 (PLA2)-dependent Ca2+ signaling in smooth muscle by cAMP- and cGMP-dependent protein kinases. Inhibitory phosphorylation of PLA2 by cyclic nucleotide-dependent protein kinases.

Both cAMP- and cGMP-dependent protein kinases inhibit agonist-stimulated phospholipase C-beta (PLC-beta) activity and inositol 1,4,5-trisphosphate-dependent Ca2+ release in vascular and visceral smooth muscle. In smooth muscle of the intestinal longitudinal layer, however, the initial steps in Ca2+ mobilization involve activation of cytosolic PLA2 (cPLA2) and arachidonic acid (AA)-dependent stimulation of Ca2+ influx. The present study examined whether cAMP- and cGMP-dependent protein kinases are capable of regulating these processes also. Agents that activated cAMP-dependent protein kinase (5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole 3',5'-cyclic monophosphothioate (Sp-isomer) and isoproterenol), cGMP-dependent protein kinase (8-(4-chlorophenylthio)-guanosine 3',5'-cyclic monophosphate and Na nitroprusside), or both kinases (vasoactive intestinal peptide and isoproterenol >1 microM) induced phosphorylation of cPLA2 and inhibition of agonist-stimulated cPLA2 activity. Phosphorylation and inhibition of cPLA2 activity by cAMP- and cGMP-dependent protein kinases were blocked by the corresponding selective inhibitors (cAMP-dependent protein kinase, N-[2(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide hydrochloride (H-89) and myristoylated protein kinase inhibitor () amide; cGMP-dependent protein kinase, (8R,9S, 11S)-(-)-9-methoxy-carbamyl-8-methyl-2,3,9,10-tetrahydro-8, 11-epoxy-1H,8H,11H,-2,7b,11a-trizadizobenzo(a,g)cycloocta(c, d, e)-trinden-1-one (KT-5823)). In contrast, AA-stimulated Ca2+ influx was inhibited by agents that activated cGMP-dependent protein kinase only; the inhibition was selectively blocked by KT-5823. The study provides the first evidence of inhibitory phosphorylation of cPLA2 in vivo by cAMP- and cGMP-dependent protein kinases. Inhibition of cPLA2 activity and AA-induced Ca2+ influx partly account for the ability of cAMP-dependent protein kinase and/or cGMP-dependent protein kinase to cause relaxation. Their importance resides in their location at the inception of the Ca2+ signaling cascade.

Alkaloids↗
PubMed1998

Selective expression of vasoactive intestinal peptide (VIP)2/pituitary adenylate cyclase-activating polypeptide (PACAP)3 receptors in rabbit and guinea pig gastric and tenia coli smooth muscle cells.

In both functional and radioligand binding studies of gastric smooth muscle from rabbit and guinea pig, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) show equal potency indicating that the receptor type is either a VIP1/PACAP2 or a VIP2/PACAP3 receptor. We have characterized the VIP/PACAP receptor expressed in freshly dispersed and cultured gastric and tenia coli smooth muscle cells of rabbit and guinea pig by reverse transcriptase-polymerase chain reaction (RT-PCR), Northern analysis, and cloning of the first extracellular domain. Specific primers based on cDNA sequences for rat VIP1/PACAP2, VIP2/PACAP3 and PACAP1 receptors were designed spanning the first extracellular domain. A 275 base pair product corresponding to VIP2/PACAP3 receptor was amplified by RT-PCR in muscle cells from both species. No RT-PCR product was obtained with primers for VIP1/PACAP2 and PACAP1 receptors. The deduced amino acid sequences showed 90% similarity in rabbit and 77% in guinea pig to the sequence in rat. The location of the aspartate, tryptophan and glycine residues and all six N-terminal cysteines required for VIP binding were conserved. The sequence in guinea pig tenia coli differed from that in guinea pig stomach by two amino acid residues, Phe40 and Phe41. Northern analysis revealed a single 3.9 kilobase (kb) mRNA corresponding to VIP2/PACAP3 receptors in rabbit and a 2.1 kb mRNA in guinea pig gastric and tenia coli muscle cells. We conclude that only VIP2/PACAP3 receptors are expressed in smooth muscle cells of rabbit and guinea pig. The two amino acid difference in the sequence obtained from guinea pig tenia coli may reflect the distinct binding and functional properties of this tissue.

Amino Acid Sequence↗
PubMed1998

Coexpression of ligand-gated P2X and G protein-coupled P2Y receptors in smooth muscle. Preferential activation of P2Y receptors coupled to phospholipase C (PLC)-beta1 via Galphaq/11 and to PLC-beta3 via Gbetagammai3.

P2 receptor subtypes and their signaling mechanisms were characterized in dispersed smooth muscle cells. UTP and ATP stimulated inositol 1,4,5-triphosphate formation, Ca2+ release, and contraction that were abolished by U-73122 and guanosine 5'-O-(3-thio)diphosphate, and partly inhibited (50-60%) by pertussis toxin (PTX). ATP analogs (adenosine 5'-(alpha, beta-methylene)triphosphate, adenosine 5'-(beta, gamma-methylene)triphosphate, and 2-methylthio-ATP) stimulated Ca2+ influx and contraction that were abolished by nifedipine and in Ca2+-free medium. Micromolar concentrations of ATP stimulated both Ca2+ influx and Ca2+ release. ATP and UTP activated Gq/11 and Gi3 in gastric and aortic smooth muscle and heart membranes, Gq/11 and Gi1 and/or Gi2 in liver membranes, and Go and Gi1-3 in brain membranes. Phosphoinositide hydrolysis stimulated by ATP and UTP was mediated concurrently by Galphaq/11-dependent activation of phospholipase (PL) C-beta1 and Gbetagammai3-dependent activation of PLC-beta3. Phosphoinositide hydrolysis was partially inhibited by PTX or by antibodies to Galphaq/11, Gbeta, PLC-beta1, or PLC-beta3, and completely inhibited by the following combinations (PLC-beta1 and PLC-beta3 antibodies; Galphaq/11 and Gbeta antibodies; PLC-beta1 and Gbeta antibodies; PTX with either PLC-beta1 or Galphaq/11 antibody). The pattern of responses implied that P2Y2 receptors in visceral, and probably vascular, smooth muscle are coupled to PLC-beta1 via Galphaq/11 and to PLC-beta3 via Gbetagammai3. These receptors co-exist with ligand-gated P2X1 receptors activated by ATP analogs and high levels of ATP.

Adenosine Monophosphate↗
PubMed1998

Longitudinal smooth muscle of the mammalian intestine. A model for Ca2+ signaling by cADPR.

Ca2+ mobilization in muscle cells from the circular muscle layer of the mammalian intestine is mediated by IP3-dependent Ca2+ release. Ca2+ mobilization in muscle from the adjacent longitudinal muscle layer involves a distinct, phosphoinositide-independent pathway. Receptors for contractile agonists in longitudinal muscle cells are coupled via a pertussis toxin-sensitive G protein to activation of PLA2 and formation of arachidonic acid (AA). The latter activates Cl- channels resulting in depolarization of the plasma membrane and opening of voltage-sensitive Ca2+ channels. Ca2+ influx via these channels induces Ca2+ release by activating sarcoplasmic ryanodine receptor/Ca2+ channels. The increase in [Ca2+]i activates membrane-bound ADP ribosyl cyclase, and the resultant formation of cADPR enhances Ca(2+)-induced Ca2+ release.

Adenosine Diphosphate Ribose↗
PubMed1998

Regulation of adenylyl cyclase type V/VI in smooth muscle: interplay of inhibitory G protein and Ca2+ influx.

The characteristics of inhibitory regulation of adenylyl cyclase V/VI by Ca2+ and G proteins were examined in dispersed gastric smooth muscle cells. The mechanisms were evoked separately, sequentially, or concurrently using ligand-gated and G protein-coupled receptor agonists and receptor-independent probes (e. g, thapsigargin). During the initial phase of agonist stimulation, alpha,beta-methylene-ATP, UTP, and ATP inhibited forskolin-stimulated cAMP formation in a concentration-dependent fashion. Inhibition by alpha,beta-methylene-ATP, which activates ligand-gated P2X receptors, was abolished by zero Ca2+, whereas inhibition by UTP, which activates P2Y2 receptors coupled to Gq/11 and Gi3, was not affected by zero Ca2+ but was abolished by pertussis toxin (PTX). Inhibition by ATP, which activates both P2X and P2Y2 receptors, was not affected by zero Ca2+ alone; but after inhibition mediated by Galphai3 was blocked with PTX, inhibition by Ca2+ influx was unmasked and was abolished by zero Ca2+. Inhibition by cholecystokinin-8 was observed only during the phase of capacitative Ca2+ influx and was blocked by zero Ca2+. Inhibition by UTP during this phase was not affected by zero Ca2+ alone; but after inhibition mediated by Galphai3 was blocked with PTX, inhibition by Ca2+ influx was unmasked and was abolished by zero Ca2+. Inhibition of adenylyl cyclase V/VI activity in smooth muscle can be mediated independently by inhibitory G proteins and Ca2+ influx but is exclusively mediated by inhibitory G proteins when both mechanisms are triggered.

Adenosine Triphosphate↗
PubMed1998

cGMP-mediated Ca2+ release from IP3-insensitive Ca2+ stores in smooth muscle.

Recent studies on the role of nitric oxide (NO) in gastrointestinal smooth muscle have raised the possibility that NO-stimulated cGMP could, in the absence of cGMP-dependent protein kinase (PKG) activity, act as a Ca(2+)-mobilizing messenger [K. S. Murthy, K.-M. Zhang, J.-G. f1p4 J. T. Grider, and G. M. Makhlouf. Am. J. Physiol. 265 (Gastrointest. Liver Physiol. 28): G660-G671, 1993]. This notion was examined in dispersed gastric smooth muscle cells with 8-bromo-cGMP (8-BrcGMP) and with NO and vasoactive intestinal peptide (VIP), which stimulate endogenous cGMP. In muscle cells treated with cAMP-dependent protein kinase (PKA) and PKG inhibitors (H-89 and KT-5823), 8-BrcGMP (10 microM), NO (1 microM), and VIP (1 microM) stimulated 45Ca2+ release (21 +/- 3 to 30 +/- 1% decrease in 45Ca2+ cell content); Ca2+ release stimulated by 8-BrcGMP was concentration dependent with an EC50 of 0.4 +/- 0.1 microM and a threshold of 10 nM. 8-BrcGMP and NO increased cytosolic free Ca2+ concentration ([Ca2+]i) and induced contraction; both responses were abolished after Ca2+ stores were depleted with thapsigargin. With VIP, which normally increases [Ca2+]i by stimulating Ca2+ influx, treatment with PKA and PKG inhibitors caused a further increase in [Ca2+]i that reverted to control levels in cells pretreated with thapsigargin. Neither Ca2+ release nor contraction induced by cGMP and NO in permeabilized muscle cells was affected by heparin or ruthenium red. Ca2+ release induced by maximally effective concentrations of cGMP and inositol 1,4,5-trisphosphate (IP3) was additive, independent of which agent was applied first. We conclude that, in the absence of PKA and PKG activity, cGMP stimulates Ca2+ release from an IP3-insensitive store and that its effect is additive to that of IP3.

Animals↗
PubMed1998

G protein-dependent activation of smooth muscle eNOS via natriuretic peptide clearance receptor.

In gastrointestinal smooth muscle, the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) induce relaxation by interacting with VIP2/PACAP3 receptors coupled via Gs to adenylyl cyclase and with distinct receptors coupled via Gi1 and/or Gi2 to a smooth muscle endothelial nitric oxide synthase (eNOS). The present study identifies the receptor as the single-transmembrane natriuretic peptide clearance receptor (NPR-C). RT-PCR and Northern analysis demonstrated expression of the natriuretic peptide receptors NPR-C and NPR-B but not NPR-A in rabbit gastric muscle cells. In binding studies using 125I-labeled atrial natriuretic peptide (125I-ANP) and 125I-VIP as radioligands, VIP, ANP, and the selective NPR-C ligand cANP(4-23) bound with high affinity to NPR-C. ANP, cANP-(4-23), and VIP initiated identical signaling cascades consisting of Ca2+ influx, activation of eNOS via Gi1 and Gi2, stimulation of cGMP formation, and muscle relaxation. NOS activity and cGMP formation were abolished (93 +/- 3 to 96 +/- 2% inhibition) by nifedipine, pertussis toxin, the NOS inhibitor, NG-nitro-L-arginine, and the antagonists ANP-(1-11) and VIP-(10-28). NOS activity stimulated by all three ligands in muscle membranes was additively inhibited by Gi1 and Gi2 antibodies (82 +/- 2 to 84 +/- 1%). In reconstitution studies, VIP, cANP-(4-23), and guanosine 5'-O-(3-thiotriphosphate) stimulated NOS activity in membranes of COS-1 cells cotransfected with NPR-C and eNOS. The results establish a unique mechanism for G protein-dependent activation of a constitutive NOS expressed in gastrointestinal smooth muscle involving interaction of the relaxant neuropeptides VIP and PACAP with a single-transmembrane natriuretic peptide receptor, NPR-C.

Animals↗
PubMed1998

Expression of endothelial nitric oxide synthase in human and rabbit gastrointestinal smooth muscle cells.

The aim of this study was to identify the nitric oxide synthase (NOS) isoform expressed in freshly dispersed rabbit gastric smooth muscle cells and in cultured rabbit gastric, human intestinal, and guinea pig taenia coli smooth muscle cells. RT-PCR products of the predicted size (354 bp) were obtained with endothelial NOS (eNOS)-specific primers, but not neuronal NOS (nNOS)- or inducible NOS (iNOS)-specific primers, in all smooth muscle preparations except guinea pig taenia coli. Control RT-PCR studies showed absence of the endothelial markers, platelet endothelial cell adhesion molecule-1 (PECAM-1) and vascular endothelial growth factor receptor (VEGFR), and the interstitial cell marker, c-kit, from cultures of smooth muscle cells. Cloning and sequence analysis showed that the predicted amino acid sequence (117 residues) in rabbit and human smooth muscle cells differed by only one residue from that of human eNOS. Northern blot analysis, using the PCR-generated and cloned eNOS cDNA from rabbits and humans as probes, demonstrated the expression of eNOS mRNA (4.4 kb) in both species. eNOS, but not nNOS or iNOS, transcripts were localized by in situ RT-PCR in single, freshly dispersed rabbit gastric smooth muscle cells; expression was evident in the majority of cells in each preparation. We conclude that eNOS is selectively expressed in rabbit gastric and human intestinal smooth muscle cells. The results confirm functional evidence for the existence of a constitutive NOS in smooth muscle cells of the gut in different species, except for guinea pig taenia coli.

Amino Acid Sequence↗
PubMed1997

Differential coupling of muscarinic m2 and m3 receptors to adenylyl cyclases V/VI in smooth muscle. Concurrent M2-mediated inhibition via Galphai3 and m3-mediated stimulation via Gbetagammaq.

Muscarinic m2 and m4 receptors couple preferentially to inhibition of adenylyl cyclase, whereas m1, m3, and m5 receptors couple preferentially to activation of phospholipase C-beta and in some cells to stimulation of cAMP. Smooth muscle cells were shown to express adenylyl cyclases types V and/or VI. Acetylcholine (ACh) stimulated the binding of [35S]GTPgammaS.Galpha complexes in smooth muscle membranes to Galphaq/11 and Galphai3 antibody. Binding to Galphaq/11 antibody was inhibited by the m3 receptor antagonist, 4-DAMP, and binding to Galphai3 antibody was inhibited by the m2 receptor antagonist, N,N'-bis[6[[(2-methoxyphenyl)methyl]amino]hexyl]-1,8-octanediamine tetrahydrochloride (methoctramine). The decrease in basal cAMP (35 +/- 5%) induced by ACh in dispersed muscle cells was accentuated by 4-DAMP or Gbeta antibody (55 +/- 8 to 63 +/- 6%). In contrast, methoctramine, pertussis toxin (PTx), or Galphai3 antibody converted the decrease in cAMP to increase above basal level (+28 +/- 5 to +32 +/- 6%); the increase in cAMP was abolished by 4-DAMP or Gbeta antibody. In muscle cells where only m3 receptors were preserved by selective receptor protection, ACh caused only an increase in cAMP that was abolished by 4-DAMP. Conversely, in muscle cells where only m2 receptors were preserved, ACh caused an accentuated decrease in cAMP that was abolished by methoctramine or PTx. In conclusion, m2 receptors in smooth muscle couple to inhibition of adenylyl cyclases V/VI via Galphai3, and m3 receptors couple to activation of the enzymes via Gbetagammaq/11.

Acetylcholine↗
PubMed1997

Studies on some trace and minor elements in blood. A survey of the Kalpakkam (India) population. Part II: Reference values for plasma and red cell, and correlation with coronary risk index.

Since data on the trace element levels in Indian population are lacking, we chose to conduct a survey of the Kalpakkam township population. People in the age group 40-55 were included in this study. Reference values for trace and minor elements of the blood of the Kalpakkam population were arrived at by carrying out the analysis of plasma and red cells of healthy subjects of the Kalpakkam population. Although the "reference values" for many elements were found to be normal and comparable to values available in the literature, slight deficiency with respect to Se was noticed. Subjects with high coronary risk index were also included in the study to assess the possible correlation of elemental and lipid profile. A study of box plots showed that the elements Se, Mg, Na, K, and Fe show significant differences between "high risk" coronary risk index (CRI > 5) and "no risk" (CRI < 4.5). In the plasma, the levels of Mg, Na, and K were found to be less in the high-risk group. In red cells, the amount of Se, Fe, and K were found to be significantly less in the "high-risk" group as compared to the "no-risk" group.

Adult↗
PubMed1997

Characterization of PACAP receptors and signaling pathways in rabbit gastric muscle cells.

Pituitary adenylate cyclase-activating peptide (PACAP) receptors and their signaling pathways were characterized in dispersed rabbit gastric muscle cells. 125I-PACAP-27 and 125I-vasoactive intestinal peptide (VIP) binding to muscle cells were inhibited equally by PACAP and VIP (mean inhibitory concentration 0.8 to 1.3 nM) and desensitized to the same extent (70-80%) by exposure to either peptide. PACAP, like VIP, increased cytosolic free Ca2+ and the formation of L-[3H]citrulline, NO-3/NO-2, guanosine 3',5'-cyclic monophosphate (cGMP), and adenosine 3'5'-cyclic monophosphate (cAMP) and induced relaxation (mean effective concentration 1.8 +/- 0.1 nM) that was partly inhibited by NG-nitro-L-arginine (L-NNA), VIP-(10-28), and PACAP 6-38. L-[3H]citrulline and cGMP formation were blocked by nifedipine, L-NNA, and pertussis toxin (PTx), implying activation of a G protein-coupled, Ca(2+)-calmodulin-dependent nitric oxide (NO) synthase. PACAP-induced relaxation was inhibited to the same extent (46-49%) by nifedipine, L-NNA, PTx, and the protein kinase G inhibitor KT-5823; the inhibition reflected the component of relaxation mediated by the NO-cGMP pathway. The residual relaxation was abolished by the protein kinase A inhibitor H-89. The pattern of inhibition of all responses was identical to that observed with VIP. Desensitization with VIP or PACAP abolished cAMP formation but had no effect on L-[3H]citrulline and cGMP formation induced by either peptide. Receptor protection with VIP or PACAP preserved fully all responses (L-[3H]citrulline, cGMP, and cAMP formation and relaxation) to either peptide. The complete cross-competition, cross-desensitization, cross-antagonism, and cross-protection of receptors by either VIP or PACAP are consistent with interaction of both peptides with the same receptors; the receptors consist of two classes, each coupled to a distinct signaling pathway.

Adenylate Cyclase Toxin↗
PubMed1996

Somatostatin receptor-mediated signaling in smooth muscle. Activation of phospholipase C-beta3 by Gbetagamma and inhibition of adenylyl cyclase by Galphai1 and Galphao.

In COS-7 cells, all five cloned somatostatin receptors are coupled via inhibitory G proteins to activation of an unidentified phospholipase C-beta (PLC-beta) isozyme and inhibition of adenylyl cyclase. In the present study, intestinal smooth muscle cells (SMC) that express only one receptor type, sstr3, and possess a full complement of G proteins and PLC-beta isozymes were used to identify the PLC-beta isozyme and the G proteins coupled to it and to adenylyl cyclase. Somatostatin-14 bound with high affinity to intestinal SMC; stimulated D-myo-inositol-1,4,5-trisphosphate (IP3) formation, Ca2+ release, and contraction; and inhibited forskolin-stimulated cAMP formation in a pertussis toxin-sensitive fashion. Somatostatin also stimulated phosphoinositide hydrolysis in plasma membranes. Only those somatostatin analogs that shared a high affinity for sstr3 receptors elicited muscle contraction. IP3 formation, Ca2+ release, and contraction in permeabilized SMC and phosphoinositide hydrolysis in plasma membranes were inhibited (approximately 80%) by pretreatment with antibodies to PLC-beta3 but not other PLC-beta isozymes, and by antibodies to Gbeta but not Galpha. Inhibition of cAMP formation was partially blocked by antibody to Galphai1 or Galphao and additively blocked by a combination of both antibodies. Somatostatin-stimulated [35S]GTPgammaS-Galpha complexes in plasma membranes were bound selectively by Galphai1 and Galphao antibodies. We conclude that in smooth muscle sstr3 is coupled to Gi1 and Go; the alpha subunits of both G proteins mediate inhibition of adenylyl cyclase, while the betagamma subunits mediate activation of PLC-beta3.

Adenylate Cyclase Toxin↗
PubMed1996

A new technique of arterial switch operation with in situ coronary reallocation for transposition of great arteries.

Coronary artery translocation is the most important step in achieving a successful result in arterial switch operations. Although a few centers have reported excellent results, coronary artery transfer requires a high technical expertise. We report a new technique of arterial switch operation without coronary translocation. By creating flaps in the proximal great arteries, the coronaries are transferred to the neoaorta without distortion of their original anatomic position. This technique avoids problems related to coronary translocation. Because coronary buttons are not excised, there is no need for nonviable material to be used in reconstruction of neopulmonary artery. Arterial wall is sutured to arterial wall, so postoperative bleeding is lessened. This technique can be used for any type of coronary anomaly and great arterial relationship. Coronary perfusion is well maintained. Two patients with transposition variants and ventricular septal defects have been operated on successfully with this technique. Postoperative investigations showed good coronary perfusion, without right or left ventricular outflow obstruction or leakage through the semilunar valves. This technique achieves anatomic correction for transposition of the great arteries, just as a conventional arterial switch operation does, but it avoids problems related to coronary artery translocation. We believe that it is a much simpler, more reliable, and more reproducible operation than others in current use, and it can be carried out by many cardiac surgeons with acceptable results. The early results are encouraging, although longer follow-up and more cases are essential.

Cardiac Surgical Procedures↗
PubMed1996

Stoichiometry of neurally induced VIP release, NO formation, and relaxation in rabbit and rat gastric muscle.

Vasoactive intestinal peptide (VIP) release, nitric oxide (NO) formation, and relaxation induced by nerve stimulation were examined in rabbit and rat gastric muscle. VIP stimulated NO formation in muscle strips, whereas NO stimulated VIP release. Nerve stimulation (0.025-16 Hz or 2-940 pulses) elicited frequency-dependent stimulation of VIP release, NO formation, and relaxation, all significant at two to three pulses. NG-nitro-L-arginine (L-NMA) abolished NO formation, abolished VIP release and relaxation at low frequencies, and partly inhibited them at higher frequencies. Oxyhemoglobin (oxy-Hb) inhibited VIP release and relaxation by 80% at low frequencies and 20-30% at higher frequencies. VIP-(10-28) abolished NO formation and relaxation at lower frequencies and partly inhibited them at higher frequencies; in contrast, VIP-(10-28) augmented VIP release in both species. The pattern of inhibition was similar in both species. Inhibition of maximal NO formation by VIP-(10-28) (82% in rabbit; 48% in rat) implied that a major component of NO is formed in muscle cells by the action of VIP. Thus 1) inhibition of relaxation by L-NNA reflects suppression of NO and VIP release from nerve terminals and NO formation in muscle cells, 2) inhibition by VIP-(10-28) partly reflects suppression of NO formation in muscle cells, and 3) inhibition by oxy-Hb reflects neutralization of extracellular NO and suppression of VIP release. The study demonstrates the dual origin of NO from nerves and muscle and its interplay with VIP in regulating relaxation.

Animals↗
PubMed1996

Opioid mu, delta, and kappa receptor-induced activation of phospholipase C-beta 3 and inhibition of adenylyl cyclase is mediated by Gi2 and G(o) in smooth muscle.

In neurons and transformed cell lines, opioid receptors are coupled to various signaling mechanisms involved in Ca2+ mobilization, including inhibition or activation of Ca2+ channels and phospholipase C-beta (PLC-beta), the enzyme responsible for generation of the Ca2+ mobilizing messenger inositol-1,4,5-trisphosphate [Ins(1,4,5)P3]. In the current study, we used selective PLC-beta and G protein antibodies to identify the PLC-beta isozyme activated by opioid receptors in intestinal smooth muscle and the G proteins to which the PLC-beta isozyme and adenylyl cyclase are coupled. [D-Pen2,D-Pen5]Enkephalin, a delta receptor agonist, stimulated Ins(1,4,5)P3 formation, Ca2+ release, and contraction; inhibited forskolin-stimulated cAMP formation in dispersed muscle cells; and stimulated phosphoinositide hydrolysis in plasma membranes; all of the effects were blocked by pertussis toxin. [D-Pen2,D-Pen5]Enkephalin-stimulated Ins(1,4,5)P3 formation, Ca2+ release, and contraction in permeabilized muscle cells and phosphoinositide hydrolysis in plasma membranes were selectively blocked by G beta antibody and PLC-beta 3 antibody; contractions stimulated by [D-Ala2,N-MePhe4,Gly-ol5]enkephalin, a mu receptor agonist, and U-69,593, a kappa receptor agonist, were also blocked by G beta and PLC-beta 3 antibodies. Inhibition of forskolin-stimulated cAMP formation by delta, mu, and kappa receptor agonists was partially blocked by G alpha i2 and G alpha o antibodies and additively blocked by a combination of the antibodies. The delta, mu, and kappa receptor agonists stimulated the binding of guanosine-5'-O-(3-thio)triphosphate to the alpha subunits of Gi2 and G(o) but not to the alpha subunits of other G proteins. We conclude that opioid mu, delta, and kappa receptors are selectively coupled to Gi2 and G(o) in intestinal smooth muscle. The beta gamma subunits of both G proteins activate PLC-beta 3, thereby stimulating Ins(1,4,5)P3-dependent Ca2+ release and smooth muscle contraction, whereas the alpha subunits inhibit adenylyl cyclase activity.

Adenylyl Cyclase Inhibitors↗
PubMed1996

Surgical experience of total anomalous pulmonary venous connection with mid-term follow-up in a developing country.

OBJECTIVE: To illustrate the incidence, the different age group, varied clinical presentation, incremental risk factors for surgery and follow-up results from this part of the world. EXPERIMENTAL DESIGN: Retrospective study with follow-up from 3 months to 5 years. SETTING: Institutional practice with hospitalised care. SELECTION PROCEDURE: Hospitalised patients with a diagnosis of total anomalous pulmonary venous connection. INTERVENTIONS: All patients who were diagnosed to have total anomalous pulmonary venous connection underwent corrective surgery. RESULTS: There were 20 hospital deaths postoperatively. The mean follow-up was 1.9 year. Logistic regression analysis identified age group, timing of surgery, associated anomalies preoperative symptoms, anatomical type of lesion, pulmonary artery hypertension, duration of ventilation, low cardiac output as risk factors for surgery. The mean survival time was 4-8 years. CONCLUSION: Mortality continues to be higher from this part of the world due to severe malnourishment, late presentation. Sociodemographic factors also play a major role in affecting surgical outcome apart from the identified risk factors for surgery.

Cardiac Surgical Procedures↗