Diltiazem provides higher internal mammary artery flow than nitroglycerin during coronary artery bypass grafting surgery.

OBJECTIVES: Perioperative internal mammary artery (IMA) vasospasm in patients undergoing coronary artery bypass grafting (CABG) surgery may lead to morbidity and mortality. Surgical stimulus is one of the common causes of IMA vasospasm. Preventive measures, beside treatment should be taken into consideration to obtain vasospasm free IMA. The effect of a pharmacologic agent on IMA flow when it is administered before harvesting the artery has not been documented. We designed a prospective randomized clinical study to compare the IMA free blood flows in patients receiving either diltiazem or nitroglycerin, starting infusion of study drugs before a surgical stimulus was applied to the IMA region and continuing throughout the isolation period. METHODS: Sixty patients undergoing elective CABG surgery with the left IMA received diltiazem (n=30, 0.05-0.1 mg/kg per hour) or nitroglycerin (n=30, 0.25-2.5 microg/kg per minute) in a randomized manner. Infusions of study drugs were started before applying a surgical stimulus to the IMA region and continued throughout the harvesting period. The first free flow was measured after IMA was cut above its bifurcation and the second after its distal segment was resected. Heart rate, temperature, mean arterial and central venous pressures were recorded. Data were analyzed with Student's t-test and Fischer's exact test. RESULTS: Preoperative and hemodynamic data were similar between the groups. The means of first and second IMA flows in patients treated with diltiazem (53.8+/-30.1 and 72.3+/-35.4 ml/min) were significantly higher than in those treated with nitroglycerin (25.7+/-16.2 and 48.9+/-23.8 ml/min; P=0.000, 0.004, respectively). IMA flows significantly increased after distal segment resection both in diltiazem (34%) and nitroglycerin groups (90%; P= 0.000, 0.000, respectively). CONCLUSIONS: Diltiazem infusion which started prior to harvesting provided higher IMA blood flow compared to nitroglycerin infusion. Considering the percentage of increases in flows after resection of distal segment, the most prone part to vasospasm, we assume that a certain amount of spasm occurred in IMA in spite of infusion of study drugs, such that less with diltiazem and more with nitroglycerin. Diltiazem plays more important role than nitroglycerin in the prevention of vasospasm.     

In vivo and in vitro effects of stellate ganglion blockade on radial and internal mammary arteries

OBJECTIVE: To investigate the effects of stellate ganglion blockade (SGB) on the internal mammary (IMA) and radial arteries (RA) in patients undergoing coronary artery bypass graft (CABG) surgery with in vivo and in vitro studies. DESIGN: Prospective, randomized trial. SETTING: University hospital. PARTICIPANTS: Thirty-seven patients undergoing CABG surgery. INTERVENTIONS: SGB was performed on 19 patients before anesthesia induction. Another group of 18 patients underwent surgery without SGB. Diameters of proximal RA, distal RA, and IMA were determined by Doppler ultrasonography before (T1) and after (T2) anesthesia induction. Control or blocked IMA and RA segments were obtained. Norepinephrine (NE) was applied to determine the contractile force of IMA and RA rings in a concentration-dependent manner. The maximal contractile response and the sensitivity of the vessels were compared. MEASUREMENTS AND MAIN RESULTS: The diameters of IMA and distal RA were statistically larger in the SGB group than those in the control group at T2. NE-induced maximum contraction was higher in the blocked RA rings than those in the control RA and blocked IMA rings. The sensitivity of IMA segments to NE was higher than that of RA segments in the SGB group. The control and blocked IMA segments showed similar sensitivity to NE. CONCLUSION: The present results show that SGB not only increases distal RA and IMA diameters but is also associated with in vitro differences, the mechanism of which remains to be elucidated. Therefore, SGB might be considered as an alternative to topical and systemic vasodilators for reducing vasospasm in patients undergoing CABG.     

Enzymatic and binding effects of atrial natriuretic factor in glomeruli and nephrons

Atrial natriuretic factor (ANF) has been suggested to exert a tubular effect on the mammalian nephron, perhaps in part by interacting with other hormones. In the present study, the effect of ANF was examined on glomeruli (Gm) and different renal tubule segments including medullary (MAL) and cortical thick ascending limb (CAL) and cortical (CCT), outer medullary (OMCT) and inner medullary collecting tubules (IMCT). This effect of ANF was assessed by alteration in adenylate cyclase and cGMP in the various nephron segments in the presence and absence of arginine vasopressin (AVP), parathyroid hormone (PTH) and calcitonin (SCT). An effect of ANF (10(-8) M) was not demonstrated on adenylate cyclase (fmol cAMP formed/30 min/micrograms protein) in Gm, CAL, MAL, CCT, OMCT or IMCT. Nor did ANF (10(-8) M) interfere with the effect of PTH (5 IU/ml) on the Gm (PTH 35.1 +/- 3.7 vs. PTH + ANF 32.5 +/- 1.8, NS), CAL (PTH 50.5 +/- 10.9 vs. PTH + ANF 46.2 +/- 1.4, NS) or AVP (10(-8) M) on the CCT (AVP 40.8 +/- 6.6 vs. AVP + ANF 33.0 +/- 3.1, NS), OMCT (AVP 56.0 +/- 11.8 vs. AVP + ANF 42.1 +/- 6.7, NS), IMCT (AVP 66.5 +/- 4.6 vs. AVP + ANF 53.5 +/- 7.0, NS) or MAL (AVP 15.5 +/- 1.6 vs. AVP + ANF 14.0 +/- 2.6, NS). ANF also did not affect SCT (1.5 x 10(-8) M)-induced adenylate cyclase on CCT (SCT 69.8 +/- 11.3 vs. SCT + ANF 79.9 +/- 7.2, NS). ANF (10(-8) M), however, significantly increased cGMP in the Gm (6.4 +/- 1.7 to 121.3 +/- 32.4 fmol/micrograms protein, P less than 0.001) and IMCT (0.63 +/- 0.16 to 1.46 +/- 0.29 fmol/micrograms protein, P less than 0.05). However, no effect of ANF on cGMP was observed in the CAL, CCT, OMCT, and MAL even at 10(-7) M ANF. PTH (5 IU/ml) did not alter either basal or ANF-stimulated cGMP in the Gm. Also, specific ANF binding was studied in the microdissected IMCT. Kd was 6.08 x 10(-9) M and Bmax was 8.07 x 10(-11) M.(ABSTRACT TRUNCATED AT 250 WORDS)     

Endothelium-dependent contraction and relaxation of the human and canine internal mammary artery: studies on bypass graft vasospasm.

The internal mammary artery (IMA) is the preferred conduit for coronary artery bypass graft because of superior late patency. However, IMA vasospasm may contribute to myocardial ischemia and early postoperative morbidity. To investigate mechanisms of vasospasm, we compared the reactivity of human and canine IMA segments in vitro to agonists known to release endothelium-derived contracting factor and endothelium-derived relaxing factor. Rings (4 mm in length) of human and canine IMA were studied in organ chambers. Human and canine vascular smooth muscle exhibited comparable contraction to norepinephrine (maximum = 7.55 +/- 0.63 gm and 6.4 +/- 0.90 gm, respectively) and relaxation to sodium nitroprusside. Human and canine IMAs exhibited comparable endothelium-derived relaxing factor-mediated relaxations to acetylcholine (human) and methacholine (canine). Human and canine IMA also exhibited comparable endothelium-dependent contraction to hypoxia (to 173.3% +/- 8.1% and 178.9% +/- 16.0% of initial prehypoxic tension; means +/- SEM; n = 12). Endothelium-dependent contraction to hypoxia in human and canine IMA could be attenuated by NG-monomethyl-L-arginine (10(-6) mol/L), a competitive inhibitor of L-arginine metabolism (n = 9 and n = 10 for human and canine; p less than 0.05). These studies establish that the canine is an appropriate model for study of human IMA vascular reactivity and that hypoxia can induce the release of an L-arginine-dependent, endothelium-derived contracting factor in the human and canine IMA. In vivo, the release of endothelium-derived contracting factor in response to hypoxemia may be cause of IMA vasospasm.     

Is cardiopulmonary bypass a reason for aspirin resistance after coronary artery bypass grafting?

OBJECTIVE: 'Off-pump' coronary artery bypass grafting (OPCAB) is an alternative to conventional coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB). While midterm results after OPCAB have become available, systematic studies of changes in platelet function after OPCAB are still missing. Since we have previously shown that oral aspirin treatment (100mg) does not achieve sufficient platelet inhibition in the majority of patients operated on with CPB, we hypothesized that bypass surgery without CPB (off-pump coronary artery bypass, OPCAB) causes less impairment of platelet inhibition by aspirin. The aim of this study was to investigate platelet function and the antiplatelet effect of aspirin after off-pump coronary artery bypass grafting in comparison with conventional on-pump surgery. METHODS: We compared platelet function (in vitro aggregation and thromboxane formation) before and at days 1 and 5 after coronary artery bypass grafting, performed with (n=15) or without (n=14) CPB. Oral aspirin treatment (100mg/d) was started at day 1 after surgery. RESULTS: After a 5 day oral treatment with aspirin, platelet aggregation was inhibited significantly in OPCAB-patients to 55.7+/-16.3% of control before surgery (P<0.05), whereas aggregation remained unchanged after CPB (105.8+/-26.9% of control before surgery; P>0.05). Since aspirin primarily inhibits platelet thromboxane formation, thromoboxane was determined after in vitro aggregation. According to platelet aggregation, thromboxane formation was only inhibited significantly after OPCAB (29.2+/-13.0% of control before surgery, P<0.05), but not after CPB (74.5+/-21.4% of control before surgery, P>0.05). This resistance to aspirin after CPB may be caused by an increased release of new platelets which are competent to form thromboxane, since the number of platelets decreased from 237+/-11x10(3)/microl before CPB to 174+/-13x10(3)/microl at day 1 after surgery and increased significantly the following days reaching 303+/-17x10(3)/microl at day 5. Platelet counts of patients operated on without CPB showed no significant changes (236+/-16x10(3)/microl before OPCAB, 220+/-16x10(3)/microl at day 1 and 266+/-31x10(3)/microl at day 5 after surgery). CONCLUSIONS: The antiplatelet effect of aspirin is largely impaired after CPB, but not after CABG without CPB. Hence, increased platelet turnover after CPB seems to contribute to aspirin resistance, since an increased number of platelets might be competent to form thromboxane within the dosing intervals.     

A comparative study on in vitro and in vivo effects of topical vasodilators in human internal mammary, radial artery and great saphenous vein

Objective: As an important prognostic factor of coronary artery bypass grafting (CABG), graft vasospasm can be observed in all currently used graft conduits. Radial artery (RA) vasospasm is more prone to occur in comparisons with internal mammary artery (IMA) and great saphenous vein (GSV). There is still controversy about which antispasmodic agent is superior to different grafts, especially to RA conduits. The aim of this pilot study was to investigate the relaxation response of four topical vasodilators to different in vitro grafts and how these vasodilators affect the blood flow of the vessel in situ during RA harvesting. Materials and methods: Vasodilatory properties of diltiazem, nitroglycerin, urapidil and nicorandil were compared in matched patient-specific segments of RA, IMA and GSV harvested from 12 patients. The vasodilatory response of the RA to intraradial administration of nitroglycerin, diltiazem and urapidil was compared in vivo (n=10 per group) by assessing the free blood flow of RA. Results: (1) The maximal relaxations occurring with urapidil, nitroglycerin and nicorandil in IMA, RA and SGV were significantly greater than that with diltiazem. The reactivity of all three graft conduits showed similar relaxation with nitroglycerin or with diltiazem, but the relaxation with urapidil in RA showed greater than that of IMA and GSV, and RA and GSV showed greater relaxation with nicorandil than IMA. (2) A dose of 10(-5)mol/l of nitroglycerin, urapidil and nicorandil but not diltiazem significantly inhibited the RA response to PE. (3) In vivo, urapidil and nitroglycerin significantly increased the RA blood flow, the potency of which was greater than that caused by diltiazem. Conclusions: (1) Comparing with nicorandil, urapidil and diltiazem, nitroglycerin caused a significant relaxation in all three graft vessels tested. (2) Nitroglycerin, nicorandil and urapidil were more effective in preventing RA spasm than diltiazem.     

Anterolateral right thoracotomy for mitral valve procedure after previous coronary artery bypass grafting with functioning internal mammary artery grafts

AIM: Mitral valve procedure after previous coronary artery bypass grafting (CABG) with functioning internal mammary artery (IMA) grafts has high risk. Especially, internal mammary artery grafts injury may be fatal. The anterolateral right thoracotomy affords easy access to the right atrium with minimal dissection, and minimizes the risk of injury to the IMA grafts. We reviewed our operative technique and outcome after mitral valve procedure after previous CABG with functioning IMA grafts. METHODS: Thirteen patients (11 male and 2 female, mean age of 67.7+/-8.5 years, range 54 to 80 years) underwent mitral valve replacement after previous CABG with functioning IMA grafts from march 1993 to september 2002. The mean interval between the previous CABG and the mitral valve procedure was 3.8 years (range 9 months to 8 years). Four patients had simultaneous mitral valve procedures at initial CABG (2 repairs and 2 replacements). The operation has performed through the anterolateral right thoracotomy, under ventricular fibrillation with moderate hypothermia and without cardioplesia. RESULTS: Mitral valve repair was performed in 3 patients, mitral valve replacement in 10 patients. The mean coronary bypass time was 69.1+/-16.2 min (range 45 to 98 min). The operation time was 159.3+/-29.4 min (range 120 to 219 min). Intensive care unit stay days was 1.9+/-1.6 days (range 1 to 5 days). Peak CK/CK-MB values were 555.1+/-290.4 IU/16.6+/-10.7 IU (range 176 to 924 IU/7 to 44 IU). Peak troponin I value was 9.5+/-5.2 pg/mL (range 4 to 17.8 pg/mL). There was no IMA injury and no early death. Other complications were newly arrhythmia in 3 patients, renal insufficiency in 1 patient, reoperation for bleeding in 1 patient. CONCLUSIONS: Anterolateral right thoracotomy approach, ventricular fibrillation with moderate hypothermia without cardioplesia were a safe and good method for mitral valve operation after previous CABG with functioning IMA graft.     

Vasoactive response of different parts of human internal thoracic artery to isosorbide-dinitrate and nitroglycerin: an in-vitro study.

OBJECTIVE: The left internal thoracic artery (LITA) is the most important graft for coronary artery bypass grafting (CABG). Its distal region is, however, prone to vasospasm. The effect of nitroglycerin (NTG) and isosorbide-dinitrate (ISDN) on different segments of this region was studied. METHODS: Rings of three segments of the LITA were studied: 6-9 mm proximal to the bifurcation (part A); 1-3 mm proximal to the bifurcation (part B); and 3-6 mm distal to the bifurcation (part C). After baseline, maximal contraction of the rings was achieved using 60 mmol/l of KCl, they were exposed to increasing doses of ISDN and NTG (10-100 microg/ml), and dose-response curves were recorded. RESULTS: The contractile response of part A to KCl was significantly lower than that of parts B and C (1.87+/-0.25 versus 4.05+/-0.39 and 7.64+/-0.54 g, respectively; P<0.001). Both nitrates inhibited the contractile response in a concentration-dependent manner. The relaxing effects of both nitrates on part A was most pronounced (P<0.01), with the effect of ISDN being higher than that of NTG (P<0.01). CONCLUSIONS: The region 6-9 mm proximal to the LITA bifurcation is less prone to vasospasm, and has greater relaxation responses to ISDN and NTG than the more vasospastic distal parts of the LITA. We recommend avoiding the use of the very distal part of this artery during CABG, and to use high doses of ISDN rather than NTG as an anti-spastic measure.     

The variable effects of dopamine among human isolated arteries commonly used for coronary bypass grafts

The direct actions of dopamine on human arterial coronary bypass grafts are not well known. We investigated its effects on isolated rings cut from radial arteries (RA), gastroepiploic arteries (GEA), and internal mammary arteries (IMA) harvested from patients undergoing coronary artery bypass surgery. Dopamine produced dose-dependent contractile responses in RA, an effect independent of the presence of a functional endothelium. The contractions were enhanced by the dopamine A(1) (DA(1))-receptor antagonist SCH23390, whereas they were blocked by an alpha(1)-adrenergic antagonist, prazosin. Results qualitatively similar to these were obtained in both GEA and IMA, although the contractile responses were far smaller. In RA, DA enhanced the norepinephrine (NE)-induced contraction, and this action of dopamine was enhanced by SCH23390. In GEA, small concentrations (<10(-7) mol/L) of DA attenuated the NE-induced contraction but larger concentrations did not. In IMA, DA induced a vasorelaxation on the NE-contraction only at higher concentrations (10(-6)-10(-5) mol/L). In both GEA and IMA, the dopamine-induced vasorelaxations on the NE contraction were completely inhibited by SCH23390. These results suggest that the affinities of DA for DA(1)- and alpha(1)-adrenergic receptors may explain its variable contractile and vasorelaxant effects among these arteries. IMPLICATIONS: Differing affinities of dopamine for dopamine A(1)- and alpha(1)-adrenergic receptors may lead to it having variable contractile and vasorelaxant effects among the arteries supplying grafts for coronary bypass surgery.     

乳内动脉-冠状动脉旁路移植术53例

作者对１９９４年１月～１９９６年１２月本院所作的５３例乳内动脉（ＩＭＡ）－冠状动脉旁路移植术进行了总结。全部患者均为经内科治疗效果不满意者。其中４４例发生过一次以上的心肌梗塞；１６例合并室壁瘤形成。除１例为非体外循环行单纯左ＩＭＡ与左前降支吻合外，其余均行左ＩＭＡ吻合前降支及大隐静脉序惯“蛇形”桥。全组平均做冠脉吻合口４．２８支。同期左室室壁瘤切除４例。手术死亡４例。３５例随访６个月～１年半，其中３０例症状消失，５例症状减轻，活动量增加。随访结果提示，ＩＭＡ冠脉旁路移植术可取得满意疗效。作者还对ＩＭＡ冠脉旁路移植术的技术要点、适应证等进行了讨论。     

乳内动脉—冠状动脉和移植术53例

作者对１９９４年１月－１９９６年１２月本院所作的５３例乳内动脉（ＩＭＡ）－冠状动脉旁路移植术进行了总结。全部患者均为经内科治疗效果不满意者。其中４４例发生过一次以上的心肌梗塞;１６例合并室壁瘤形成。除１例为非体外循环单纯左ＩＭＡ与左前降支史合外,其余元首地左ＩＭＡＫ吻合前降支及大陷序惯“蛇形”桥。全组平均做冠脉吻合口４．２８支。同期左室壁瘤切除４例。３５例随访６个月－１年半,其中３０例症状消失,５     

Nitric oxide and endothelium-derived hyperpolarizing factor in human arteries and veins

BACKGROUND: We have investigated and compared nitric oxide (NO) release and endothelium-derived hyperpolarizing factor (EDHF)-mediated hyperpolarization in the human internal mammary artery (IMA), radial artery (RA), saphenous vein (SV), and coronary artery. MATERIALS AND METHODS: Vessel segments taken from coronary artery bypass grafting or heart transplantation patients were placed in an organ chamber. NO-sensitive electrode or intracellular glass microelectrode was used to study NO or EDHF in response to acetylcholine (ACh) and bradykinin (BK). RESULTS: The resting membrane potential of the smooth muscle cells of IMA, RA, and SV was -58 +/- 0.84 (n = 61), -61 +/- 1.3 mV (n = 46, p = 0.03), and -62 +/- 0.9 mV (n = 23, p = 0.0001) respectively. BK- (10(-7) M) induced EDHF-mediated hyperpolarization (-10.9 +/- 1.5 mV, n = 7) in the IMA was significantly greater than that in RA (-5.8 +/- 0.9 mV, n = 6, p = 0.04) and SV (-5.1 +/- 0.5 mV, n = 8, p < 0.01). The basal release of NO in IMA (16.8 +/- 1.9 nM) was significantly higher than that in RA (11.1 +/- 1.0 nM, n = 12, p = 0.02) and in SV (9.9 +/- 2.8 nM, n = 13, p < 0.001). The stimulated release of NO to BK in IMA was significantly greater than that in RA (44.3 +/- 4.0 vs 25.8 +/- 3.6 nM, n = 8, p = 0.004). The duration of NO release was longer in IMA than in RA or in SV. CONCLUSIONS: The basal and stimulated release of NO and EDHF-mediated hyperpolarization in the IMA are significantly greater than that in the RA and SV. EDHF exists in all these human vessels. This study reveals the differences among human vessels regarding the endothelial function that have implications in vasospasm, coronary protection, or long-term graft patency.     

Effects of ketamine on K+-contracture in isolated vascular smooth muscle from rabbit

The effects of ketamine on contraction induced by depolarization of cell membrane (high K+-induced contracture) were studied in isolated vascular smooth muscle from rabbit portal vein. Ketamine in concentrations above 5 x 10(-4) M caused relaxation in phasic contraction, and above 10(-4) M caused relaxation in tonic contraction. These effects of ketamine at concentrations of between 10(-5) to 10(-3) M were dose dependent and reversible. In concentration above 10(-5) M, ketamine decreased the contractile response (tonic contraction) induced by 2.5 mM Ca2+ after the temporary contracture in Ca2+-free, high K+ solution. The contractile responses to norepinephrine (10(-6) M) or serotonin (10(-6) M) were also inhibited by ketamine. From these findings, it is concluded that ketamine decreases contractile responses due to transmembrane Ca2+ influx after depolarization of cell membrane and may decrease the contractile responses in concentration above 5 x 10(-4) due to Ca2+ release inhibition from sarcoplasmic reticulum.     

Interaction between vasodilators and vasopressin in internal mammary artery and clinical significance

BACKGROUND: Arginine vasopressin (AVP) has recently been demonstrated as an alternative in the treatment of severe refractory vasodilatation in coronary artery bypass grafting. However, AVP may be a spasmogen for graft spasm. We compared the in vitro antispastic effect among calcium-channel antagonists (nifedipine, diltiazem, and verapamil), nitroglycerin, and the highly selective AVP (V1) receptor antagonist [1-deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin. METHODS: Human internal mammary artery segments (n = 218) were studied in organ baths. The inhibitory effects of the above vasodilators on AVP-mediated contraction were studied in two ways: relaxation with AVP precontraction and depression of the AVP-induced contraction after pretreatment with vasodilators. RESULTS: All three calcium-channel antagonists caused limited relaxation (18.3%+/-5.4% for nifedipine, n = 11; 22.2%+/-3.8% for verapamil, n = 10; and 26.2%+/-7.5% for diltiazem, n = 9). The plasma concentration of calcium-channel antagonists had no significant depression effect on the AVP-induced contraction. In contrast, [1-deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin caused full (100%, n = 11) and nitroglycerin caused nearly full (93%+/-3%, n = 10) relaxation. Pretreatment with [1-deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin (10(-8), 10(-7), or 10(-6) mol/L, respectively) significantly increased the effective concentration for 50% of the AVP-induced contraction (10(-8.6)+/-10(0.1) mol/L, p = 0.009; 10(-7.8)+/-10(0.07) mol/L, p = 0.000; or 10(-6.9)+/-10(0.11) mol/L, p = 0.000 versus the control, 10(-9.24)+/-10(0.16) mol/L). However, nitroglycerin only slightly depressed the AVP-induced contraction. CONCLUSIONS: [1-Deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin may provide specific antispastic effect in either prophylaxis or treatment of the AVP-related vasospasm in the internal mammary artery. Nitroglycerin may be effective in treatment but has little effect on prophylaxis. Use of calcium-channel antagonists may have little benefit in AVP-related vasospasm.     

Dexmedetomidine produces dual alpha2-adrenergic agonist and alpha1-adrenergic antagonist actions on human isolated internal mammary artery

OBJECTIVE: To investigate the direct effects of dexmedetomidine (DEX) on isolated human internal mammary artery (IMA). DESIGN: In vitro experimental study. SETTING: Cardiovascular Pharmacology Laboratory, Department of Pharmacology, Gulhane School of Medicine, Ankara, Turkey. PARTICIPANTS: IMA segments were obtained from 18 patients undergoing coronary artery bypass surgery. INTERVENTIONS: The response in IMA was recorded isometrically by a force displacement transducer in isolated organ baths. DEX-induced contractions were tested in the presence of the alpha2-adrenoceptor antagonist yohimbine (10(-7) mol/L) and the alpha1-adrenoceptor antagonist prazosin (10(-8) M). The effect of DEX (10(-7), 10(-6), and 10(-5) mol/L) on phenylephrine (10(-9)-3 x 10(-4) mol/L)-induced contactions was also tested. MEASUREMENT AND MAIN RESULTS: DEX (10(-9) mol/L-3 x 10(-5) mol/L) caused contraction in IMA segments. The contraction at lower concentrations of DEX (10(-9) mol/L-3 x 10(-7) mol/L) was attenuated by yohimbine (10(-7) mol/L), whereas prazosin (10(-8) mol/L) attenuated the contractions at higher concentrations of DEX (10(-6) mol/L-3 x 10(-5) mol/L). Incubation of IMA segments with high concentrations of DEX (10(-6) mol/L and 10(-5) mol/L) caused an inhibition of phenylephrine (10(-9) mol/L-3 x 10(-4) mol/L)-induced contraction. CONCLUSION: These data suggest that DEX causes contraction by activating alpha2-adrenoceptors at lower concentrations, but it may also activate alpha1-adrenoceptors at higher concentrations in IMA. The action of DEX on phenylephrine-induced contraction may be related to an alpha1-adrenoceptor antagonistic effect produced via partial alpha1-adrenoceptor agonistic action.     

The cAMP system in vasopressin-sensitive nephron segments of the vitamin D-treated rat

The present study was undertaken to investigate the cAMP system in isolated vasopressin (AVP)-sensitive segments of the hypercalcemic rat. Hypercalcemia was produced by supplementation of diet with dihydrotachysterol, achieving a mean serum calcium of 12.6 mg%. Maximal urinary concentration was only 1982 +/- 119 mOsm/kg H2O in pair, watered hypercalcemic rats when compared to 2478 +/- 93 mOsm/kg H2O in controls (N = 7) (P less than 0.01). Vasopressin stimulated adenylate cyclase activity at concentrations of vasopressin between 10(-9) and 10(-7) M was indistinguishable in the outer medullary collecting duct (OMCD) and inner medullary collecting duct (IMCD) of tubules dissected from hypercalcemic rats or normocalcemic rats. Likewise, in situ cAMP accumulation in response to 10(-7) M AVP was not significantly different in either OMCD or IMCD of hypercalcemic or normocalcemic rats at either isotonic or hypertonic media conditions. In contrast, while 10(-7) M AVP significantly (P less than 0.05) increased cAMP accumulation in the medullary ascending limb (MAL) of normocalcemic rats it failed to do so in the MAL of hypercalcemic rats. This failure to accumulate cAMP appears to be due to impairment in AVP-stimulated adenylate cyclase rather than to enhanced phosphodiesterase activity. A similar decrement in glucagon stimulated adenylate cyclase occurred with 10(-6) M glucagon. The results demonstrate that in chronic hypercalcemia the cAMP system in the OMCT and IMCD of the rat is intact, but the MAL demonstrates abnormal AVP responsiveness due to impaired adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of systemic vasodilators: effects on flow in internal mammary and radial arteries

BACKGROUND: Spasm is a major concern with the use of arterial conduits in coronary artery bypass surgery (CABG). We evaluated the effect of systemic vasodilators on in vivo radial artery flow compared with internal mammary artery (IMA) flow. METHODS: Fifty patients undergoing primary CABG with a mean age of 69 +/- 5 years enrolled in this study and were randomized to 1 of 5 groups based on the vasodilating agent administered (nitroglycerin, nitroprusside, dobutamine, milrinone, and normal saline as control group). Radial artery and IMA flows, blood pressure, central venous pressure, and heart rate were measured before and 10 minutes after drug administration. RESULTS: Mean arterial pressure decreased significantly after drug administration in both the nitroglycerin (p = 0.007) and nitroprusside (p < 0.001) groups and increased in the dobutamine group (p < 0.001). There were no significant differences between IMA flow or radial flow among the groups before drug administration. A multivariate general linear model was created and revealed drug (specifically nitroglycerin) as the only predictor to increase flow in the IMA (p < 0.001) or the radial artery (p = 0.009). CONCLUSIONS: We conclude that intravenous nitroglycerin causes in vivo vasodilatation of both the IMA and radial artery and is a good systemic vasodilator to be given when harvesting these two conduits.     

Clinical performance and biocompatibility of poly(2-methoxyethylacrylate)-coated extracorporeal circuits

BACKGROUND: Vascular endothelial growth factor (VEGF) has been shown to have potential to treat ischemic diseases. Moreover, its vasorelaxing or vasodilatory effect might be favorable for relieving graft spasm. In this study, we examined the vasorelaxing effects of recombinant VEGF in isolated human internal mammary artery (IMA) and compared the responses to acetylcholine and nitroglycerin. METHODS: Isometric tension of IMA ring segments was measured with an organ bath technique. With an optimal resting tension determined from its individual length-tension curve, precontraction was induced by 10(-8) M U46619 and cumulative concentration-relaxation was measured by application of VEGF (10(-12) to 10(-15) M), acetylcholine (10(-10) to 10(-5) M), and then nitroglycerin (10(-4.5) M). RESULTS: Vascular endothelial growth factor induced concentration-dependent relaxation (EC50: -9.89+/-0.05 log M; Emax: 63.2%+/-7.3%) in IMA with intact endothelium. The relaxant responses to VEGF were significantly attenuated by pretreatment with Nomega-nitro-L-arginine (L-NNA) alone and indomethacin + L-NNA, and totally abolished by removal of the endothelium or pretreatment with indomethacin + L-NNA + oxyhemoglobin. Internal mammary arteries became more sensitive to VEGF in the presence of indomethacin alone. However, acetylcholine-induced relaxation was not abolished by treatment with indomethacin + L-NNA + oxyhemoglobin (Emax: 16.9%+/-2.7%). The endothelium-independent relaxations induced by nitroglycerin were also significantly inhibited by administration of oxyhemoglobin. CONCLUSIONS: The results demonstrate that VEGF-induced endothelium-dependent relaxation in the human IMA is mainly due to nitric oxide release. Although the vasorelaxing effect is not the primary advantage of this drug when it is used for angiogenesis, such effect may be advantageous in patients who also need a coronary artery bypass operation.     

Pharmacological studies on internal mammary artery bypass grafts. Action of endogenous and exogenous vasodilators and vasoconstrictors

BACKGROUND: The purpose of this experiment was four-fold: 1) to determine the effect of currently used cardiovascular drugs on internal mammary artery (IMA) vascular tone, 2) to examine IMA reactivity to autacoids and products released from aggregating platelets, 3) to compare the vascular reactivity of the right versus left IMA, and 4) to determine whether the canine IMA was an acceptable physiological model as regards its similarity to the human IMA, which is used routinely for coronary artery bypass grafting. METHODS: To study factors that modulate the tone of IMA, bypass grafts, right and left canine IMAs were studied in vitro in organ chambers (95% O(2)/5% CO(2), pH=7.4). RESULTS: Increasing concentrations (10(-9) to 10(-4M)) of the neurotransmitter acetylcholine (ACH) and the platelet-derived products adenosine diphosphate (ADP) or serotonin (5-HT) induced vasodilatation of contracted right and left IMAs. The vasodilation caused by ACH and ADP was endothelium-dependent while serotonin acted directly on the vascular smooth muscle. Histamine and bradykinin also induced IMA vasodilation, histamine via a direct action on the smooth muscle, and bradykinin through the release of nitric oxide (NO). In canine IMAs, the calcium ionophore A23187 produced endothelium-dependent vasodilation of contracted blood vessels; this vasodilation was blocked by N(G)-nitro-L-arginine (10(-4)M), a competitive inhibitor of nitric oxide synthesis from L-arginine, and by hemoglobin (10(-5)M). Dopamine, dobutamine, and papaverine induced vasodilation of the IMA regardless of the presence or absence of an intact intima, while norepinephrine induced profound IMA vasoconstriction, which was comparable to contraction to potassium ions or the constrictor peptide endothelin. CONCLUSIONS: These experiments establish a pharmacological profile of IMA and demonstrate that endogenous and exogenous compounds can significantly alter its vascular tone.     

The history and evolution of coronary artery bypass grafting

It is nearly 40 years since the introduction of coronary artery bypass grafting (CABG) in humans. A. Carrel (1910) attempted the first CABG in animals and G. Murray (1954) succeeded in performing experimental CABG using the internal mammary artery (IMA). The first reported CABG using the IMA in humans was performed by R. Goetz using the sutureless technique in 1960. V. Kolessov (1964) performed the first sutured bypass grafting using the IMA. From 1962 to 1967, human CABG using autogenous saphenous vein grafts was performed by D. Sabiston (1962). H. Garrett (1964), D. Kahn (1966), and R. Favaloro (1967). Saphenous vein grafting became the most common CABG technique for the next two decades. In Japan, Y. Sezai et al. performed CABG using the free femoral artery, we performed CABG using the IMA, and S. Asada et al. performed CABG using the saphenous vein in 1970. In 1986, F. Loop et al. reported that the long-term survival rate of CABG was significantly higher when the IMA rather than the saphenous vein was used. IMA grafting, supplemented by the gastroepiploic artery, inferior epigastric artery, and radial artery, has enabled complete arterial revascularization to be performed in almost all patients. In the graft selection for CABG, the first choice is the left IMA and the second choice is the right IMA. The third choice is the gastroepiploic artery and/or radial artery, depending on the target anastomotic site, degree of stenosis, size of the distal graft, and in situ or free use.