Methods for treating pulmonary hypertension and compositions comprising vasoactive intestinal peptide

Abstract

A method and device for discharging an electrical defibrillation pulse or an electrical demand pacer pulse or delivering at least one pharmaceutical agent to treat conditions such as cardiac arrest, bradycardia, arrhythmia, cardiac standstill, PEA, EMD and other heart conditions are disclosed. The pharmaceutical agent can be delivered into the heart tissue, the heart cavity, or the peritoneal cavity. The pharmaceutical agent can also include analgesics such as morphine. Also included are pharmaceutical agents used to increase myocardial contractility or inhibit platelet aggregation and vasoactive intestinal polypeptide (VIP) and thyroid hormones such as T3 and T4 can be delivered. A method for the treatment of cardiac arrest or pulmonary hypertension patients by administering a therapeutically effective amount of vasoactive intestinal polypeptide is also encompassed by the invention.

1 . An apparatus for restarting or regulating the contractions of a heart having a septum, heart tissue, a heart cavity and a peritoneal cavity comprising: a catheter having an electrically nonconductive probe having a proximal end and a distal portion terminating in a tip; an electrically conductive pathway capable of transmitting an electrical signal through said probe, which electrical signal includes an electrical defibrillation pulse or an electrical demand pacer pulse; a defibrillator means electrically coupled at said tip of said probe with said electrically conductive pathway for anchoring said probe to the septum and for transmitting an electrical pulse sufficient to affect heart contractions; a sensor for detecting mechanical activity of the heart; and a drug delivery system capable of delivering a pharmaceutical agent capable of affecting the contractions of the heart; wherein the sensor is functionally coupled to the defibrillator and the drug delivery system such that, if upon defibrillation, the heart fails to resume normal mechanical activity, the sensor signals the drug delivery system to deliver a preset amount of the pharmaceutical agent to the heart. 
     
     
         2 . The apparatus according to  claim 1  wherein the drug delivery system comprises: a drug reservoir for storing the pharmaceutical agent; and a drug catheter through which fluid is transported from the drug reservoir to the heart tissue, the heart cavity or the peritoneal cavity. 
     
     
         3 . The apparatus according to  claim 1  further comprising an analyzer for determining whether an electrical defibrillation pulse, an electrical demand pacer pulse, or the pharmaceutical agent, or a combination thereof is required for restarting or controlling the contractions of the heart. 
     
     
         4 . The apparatus according to  claim 3  further comprising a monitoring system for coordinating the sensor, the analyzer, the discharge of the electrical defibrillation pulse or the electrical demand pacer pulse and delivery of the pharmaceutical agent and recording the contractions of lack of contractions of the heart and the effect of said discharge or said delivery on the heart. 
     
     
         5 . The apparatus according to  claim 1  wherein the pharmaceutical agent includes VIP, analogue or derivative thereof, or a thyroid hormone, analogue or derivative thereof 3b 
     
     
         6 . The apparatus according to  claim 1  wherein the pharmaceutical agent includes epinephrine, atropine, sodium bicarbonate and lidocaine. 
     
     
         7 . The apparatus according to  claim 1  wherein the pharmaceutical agent includes an analgesic. 
     
     
         8 . The apparatus according to  claim 1  wherein the pharmaceutical agent increases myocardial contractility. 
     
     
         9 . The apparatus according to  claim 1  a controller for controlling the discharge of an electrical defibrillation pulse or an electrical demand pacer pulse, or the delivery at least one pharmaceutical agent. 
     
     
         10 . A method for restarting or regulating the contractions of a heart having a septum, heart tissue, a heart cavity and a peritoneal cavity comprising the following steps: sensing and analyzing the contractions or lack of contractions of the heart; determining whether an electrical defibrillation pulse or an electrical demand pacer pulse or a pharmaceutical agent capable of affecting the contractions of the heart can restart or regulate the contractions of the heart; discharging the electrical defibrillation pulse or the electrical demand pacer pulse into the septum, or delivering the pharmaceutical agent to the heart tissue, the heart cavity or the peritoneal cavity; monitoring the contractions of lack of contractions of the heart; and if necessary, repeating the steps. 
     
     
         11 . The method according to  claim 10  wherein the pharmaceutical agent includes a VIP, analogue or derivative thereof, or a thyroid hormone, analogue or derivative thereof. 
     
     
         12 . The method according to  claim 10  wherein the pharmaceutical agent includes epinephrine, atropine, sodium bicarbonate and lidocaine. 
     
     
         13 . The method according to  claim 10  wherein the pharmaceutical agent includes an analgesic. 
     
     
         14 . The method according to  claim 10  wherein the pharmaceutical agent increases myocardial contractility. 
     
     
         15 . A kit for use in restarting or regulating the contractions of a heart comprising: a system for delivering a therapeutically effective amount of a pharmaceutical agent capable of affecting the contractions of the heart; a system for discharging an electrical defibrillation pulse or an electrical demand pacer pulse; and a sensor for determining the effect of defibrillation on the mechanical activity of the heart and initiating delivery of the pharmaceutical agent if necessary. 
     
     
         16 . The kit according to  claim 15  wherein the pharmaceutical agent includes at least one a VIP or a derivative. thereof; a thyroid hormone or a derivative thereof; epinephrine, atropine, sodium bicarbonate and lidocaine; an analgesic; or a substance which increases myocardial contractility. 
     
     
         17 . The kit according to  claim 15  wherein the system for delivering the therapeutically effective amount includes: a drug reservoir for storing the pharmaceutical agent; or a drug catheter through which fluid is transported from the drug reservoir to the heart tissue; or a drug catheter through which fluid is transported from the drug reservoir to the heart cavity; or a drug catheter through which fluid is transported from the drug reservoir to the peritoneal cavity; or a combination thereof. 
     
     
         18 . The kit according to  claim 15  wherein the system for discharging an electrical defibrillation pulse or an electrical demand pacer pulse includes: a catheter having an electrically nonconductive probe having a proximal end and a distal portion terminating in a tip; an electrically conductive pathway capable of transmitting an electrical signal through said probe, which electrical signal includes an electrical defibrillation pulse or an electrical demand pacer pulse; and a defibrillator means electrically coupled at said tip of said probe with said electrically conductive pathway for anchoring said probe to the heart and for transmitting an electrical pulse sufficient to affect the contractions of the heart. 
     
     
         19 . A method for restarting or regulating the contractions of a heart having a septum, heart tissue, a heart cavity, a right ventricular cavity and a peritoneal cavity comprising the following steps: (a) applying a defibrillation current to the heart tissue with a device having a catheter; (b) detecting the presence of a pulse or mechanical activity; (c) activating a mechanical activity sensor; (d) detecting the presence or absence of contractile activity; and (e) administering an appropriate dose of an inotropic agent. 
     
     
         20 . The method according to  claim 19  wherein detecting the presence of a pulse or mechanical activity occurs by measuring a change of impedance in the catheter, or detecting a pulse wave by ultrasound. 
     
     
         21 . The method according to  claim 20  wherein the change of impedance is measured by passing a known voltage through the catheter and measuring electrical resistance. 
     
     
         22 . The method according to  claim 20  wherein detecting the pulse wave comprises using at least two transducers measuring a change in distance between the transducers. 
     
     
         23 . The method of  claim 19  wherein the inotropic agent is delivered into the right ventricular cavity. 
     
     
         24 . A method of reversing the buildup of rT3 in a patient and post cardiac arrest in a patient comprising injecting an inotropic agent into the right ventricular cavity of the heart of the patient. 
     
     
         25 . The method according to  claim 24  wherein the inotropic agent is administered by using a device having a catheter and a pump, wherein said pump contains the inotropic agent and is activated after administering a defibrillation pulse and detecting the absence of mechanical activity of the heart. 
     
     
         26 - 40 . (canceled) 
     
     
         41 . A kit for use in a method for treatment of patients with secondary pulmonary hypertension, wherein said kit comprises a unit dose of a composition of vasoactive intestinal peptide packaged and ready for use, a suitable method for administration of the composition of vasoactive intestinal peptide, and optional written instructions. 
     
     
         42 . (canceled) 
     
     
         43 . A method for treatment of a patient with cardiac arrest, comprising administering to the patient a composition comprising an amount of vasoactive intestinal polypeptide, or a pharmaceutically acceptable salt thereof, analogues thereof, or vasoactive intestinal polypeptide-like peptides, sufficient to ameliorate the cardiac arrest. 
     
     
         44 . The method according to  claim 43  wherein the treatment restores cardiac function. 
     
     
         45 . The method according to  claim 44  wherein the vasoactive intestinal polypeptide is administered by direct injection into a heart cavity of the patient. 
     
     
         46 . The method according to  claim 44  wherein the vasoactive intestinal polypeptide is administered by parenteral injection. 
     
     
         47 . The method according to  claim 46  wherein the vasoactive intestinal polypeptide is administered by parenteral intravenous injection. 
     
     
         48 . The method according to  claim 46  wherein the vasoactive intestinal polypeptide is administered by direct parenteral intravenous injection into a central venous line of the patient. 
     
     
         49 . The method according to  claim 44  wherein the vasoactive intestinal polypeptide is administered directly to the pulmonary system of the patient. 
     
     
         50 . The method according to  claim 49  wherein the vasoactive intestinal polypeptide is administered directly to the pulmonary system by direct endotracheal injection. 
     
     
         51 . The method according to  claim 44  wherein the vasoactive intestinal polypeptide is administered directly to the pulmonary system by way of infusion through a respiratory airway of the patient. 
     
     
         52 . The method according to  claim 43  wherein the vasoactive intestinal polypeptide is administered by at least one rapid bolus injection. 
     
     
         53 . The method according to  claim 43  wherein the vasoactive intestinal polypeptide is present in an amount between 500 μg and 10 g. 
     
     
         54 . The method according to  claim 43  wherein the composition comprises vasoactive intestinal polypeptide at a concentration of 5 g/ml. 
     
     
         55 . The method according to  claim 43 , wherein the peptide is an analogue of vasoactive intestinal polypeptide, or a vasoactive intestinal polypeptide-like peptide. 
     
     
         56 . The composition according to  claim 55 , wherein the composition comprises VIP with a liquid excipient selected from the group consisting of water, saline, glycerol or ethanol, optionally with an appropriate pharmaceutical and medicinal agent. 
     
     
         57 . A method for treating a patient with cardiac failure due to a disease, comprising administering to the patient a composition comprising vasoactive intestinal polypeptide in an amount sufficient to restore cardiac function. 
     
     
         58 . The method according to  claim 57  wherein the vasoactive intestinal polypeptide is administered by direct injection into a heart cavity of the patient. 
     
     
         59 . The method according to  claim 57  wherein the vasoactive intestinal polypeptide is administered by parenteral injection. 
     
     
         60 . The method according to  claim 59  wherein the vasoactive intestinal polypeptide is administered by parenteral intravenous injection. 
     
     
         61 . The method according to  claim 59  wherein the vasoactive intestinal polypeptide is administered by direct parenteral intravenous injection into a central venous line of the patient. 
     
     
         62 . The method according to  claim 57  wherein the vasoactive intestinal polypeptide is administered directly to the pulmonary system of the patient. 
     
     
         63 . The method according to  claim 62  wherein the vasoactive intestinal polypeptide is administered directly to the pulmonary system by direct endotracheal injection. 
     
     
         64 . The method according to  claim 62  wherein the vasoactive intestinal polypeptide is administered directly to the pulmonary system by way of infusion through a respiratory airway of the patient. 
     
     
         65 . The method according to  claim 57 , wherein the vasoactive intestinal polypeptide is administered by at least one rapid bolus injection. 
     
     
         66 . The method according the  claim 57  wherein the vasoactive intestinal polypeptide is present in an amount between 500 μg and 10 g. 
     
     
         67 . The method according the  claim 57  wherein the composition comprises vasoactive intestinal polypeptide at a concentration of 5 g/ml. 
     
     
         68 . A method for treatment of a patient with cardiac electrical standstill, comprising administering a composition comprising vasoactive intestinal polypeptide in an amount sufficient to restore effective cardiac function. 
     
     
         69 . The method according to  claim 68  wherein the vasoactive intestinal polypeptide is administered by direct injection into a heart cavity of the patient. 
     
     
         70 . The method according to  claim 68  wherein the vasoactive intestinal polypeptide is administered by parenteral injection. 
     
     
         71 . The method according to  claim 68  wherein the vasoactive intestinal polypeptide is administered by parenteral intravenous injection. 
     
     
         72 . The method according to  claim 68  wherein the vasoactive intestinal polypeptide is administered by parenteral intravenous injection into a central venous line of the patient. 
     
     
         73 . The method according to  claim 68  wherein the vasoactive intestinal polypeptide is administered directly to the pulmonary system of the patient. 
     
     
         74 . The method according to  claim 73  wherein the vasoactive intestinal polypeptide is administered directly to the pulmonary system by direct endotracheal injection. 
     
     
         75 . The method according to  claim 73  wherein the vasoactive intestinal polypeptide is administered directly to the pulmonary system by way of infusion through a respiratory airway of the patient. 
     
     
         76 . The method according to  claim 68  wherein the vasoactive intestinal polypeptide is administered by at least one rapid bolus injection. 
     
     
         77 . The method according the  claim 68  wherein the vasoactive intestinal polypeptide is present in an amount between 500 μg and 10 g. 
     
     
         78 . The method according the  claim 68  wherein the composition comprises vasoactive intestinal polypeptide at a concentration of 5 g/ml. 
     
     
         79 . A method for treatment of a patient with spontaneous cardiac failure resulting from electro-mechanical dissociation comprising administering a composition comprising vasoactive intestinal polypeptide in an amount sufficient to restore a cardiac rhythm. 
     
     
         80 . The method according to  claim 79  wherein the cardiac rhythm is a normal sinus rhythm. 
     
     
         81 . The method according to  claim 79  wherein the vasoactive intestinal polypeptide is administered by direct injection into a heart cavity of the patient. 
     
     
         82 . The method according to  claim 79  wherein the vasoactive intestinal polypeptide is administered by parenteral injection. 
     
     
         83 . The method according to  claim 82  wherein the vasoactive intestinal polypeptide is administered by parenteral intravenous injection. 
     
     
         84 . The method according to  claim 82  wherein the vasoactive intestinal polypeptide is administered by parenteral intravenous injection into a central venous line of the patient. 
     
     
         85 . The method according to  claim 82  wherein the vasoactive intestinal polypeptide is administered directly to the pulmonary system of the patient. 
     
     
         86 . The method according to  claim 85  wherein the vasoactive intestinal polypeptide is administered directly to the pulmonary system by direct endotracheal injection. 
     
     
         87 . The method according to  claim 87  wherein the vasoactive intestinal polypeptide is administered directly to the pulmonary system by way of infusion through a respiratory airway of the patient. 
     
     
         88 . The method according to  claim 79 , wherein the vasoactive intestinal polypeptide is administered by at least one rapid bolus injection. 
     
     
         89 . The method according the  claim 79  wherein the vasoactive intestinal polypeptide is present in an amount between 500 μg and 10 g. 
     
     
         90 . The method according the  claim 79  wherein the composition comprises vasoactive intestinal polypeptide at a concentration of 5 g/ml. 
     
     
         91 . A kit for use in the treatment of cardiac arrest patients, comprising a therapeutically effective amount of a composition of VIP, a method for administration of the composition of VIP, and optional written instructions for the use of the kit. 
     
     
         92 . A kit according to  claim 91  wherein the VIP is packaged into single dose units for administration.